Patent application title: PROBE INCLUDING FALSE-POSITIVE-SUPPRESSING FUNCTION, METHOD FOR DESIGNING THE SAME, AND METHOD FOR UTILIZING THE SAME
Inventors:
IPC8 Class: AC12Q16876FI
USPC Class:
1 1
Class name:
Publication date: 2019-12-05
Patent application number: 20190367981
Abstract:
An object of the present invention is to provide a means for detecting or
quantitatively determining short-chain nucleic acids by simple
double-strand formation with high specificity.
The present invention relates to a polynucleobase probe including, in a
sequence complementary to a target sequence having at least one sequence
of any one of SEQ ID NOs: 1 to 10, a sequence in which at least one of
bases in a portion complementary to any one sequence of SEQ ID NOs: 1 to
10 in the target sequence becomes abasic and/or is substituted; a method
for designing the same; and a method for utilizing the same.Claims:
1. A polynucleobase probe comprising: in a sequence complementary to a
target sequence having at least one sequence of any one of SEQ ID NOs: 1
to 10, a sequence in which at least one of bases in a portion
complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target
sequence becomes abasic and/or is substituted; and/or a sequence which is
cleaved to have, on an end, at least one sequence complementary to a
sequence of 2 bases or less in any one sequence of SEQ ID NOs: 1 to 10 in
the target sequence.
2. The polynucleobase probe according to claim 1, which is 10- to 50-mer.
3. The polynucleobase probe according to claim 2, which is 15- to 28-mer.
4. The polynucleobase probe according to claim 1, to which a label is bound.
5. The polynucleobase probe according to claim 1, wherein, in the portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence, at least one of the bases which become abasic or are substituted is located inside the portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence.
6. The polynucleobase probe according to claim 1, wherein, in the sequence complementary to any one sequence of SEQ ID NOs: I to 10 in the target sequence, a ratio of at least one of the bases which become abasic or are substituted with respect to any one of 3 to 5 guanines and cytosines is 1.
7. The polynucleobase probe according to claim 1, wherein the target nucleic acid is a 10- to 50 mer DNA or RNA.
8. The polynucleobase probe according to claim 7, wherein the target nucleic acid is a miRNA.
9. The polynucleobase probe according to claim 1, which is a DNA, RNA, LNA, GNA, BNA, or PNA.
10. A method for designing a polynucleobase probe sequence which is capable of binding to a target sequence having at least one sequence of any one of SEQ ID NOs: 1 to 10 with high specificity, the method comprising: A) selecting a 10- to 50-mer sequence fully complementary to the target sequence as a. fully complementary probe sequence; and B) (i) in the fully complementary probe sequence, designing the polynucleobase probe sequence by substituting and/or making at least one of bases abasic in a portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence, and/or in the fully complementary probe sequence, designing the polynucleobase probe sequence by cleaving an end of the fully complementary probe sequence such that a portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence becomes 2 bases or less.
11. A method for detecting or quantitatively determining a target nucleic acid having at least one sequence of any one of SEQ ID NOs: 1 to 10 in a test sample with high specificity, the method comprising: preparing the test sample to detect the target nucleic acid; bringing at least one kind of the polynucleobase probes according to claim 1 in contact with the test sample; and detecting or quantitatively determining the target nucleic acid bound to the polynucleobase probe.
12. The polynucleobase probe according to claim 3, wherein, in the portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence, at least one of the bases which become abasic or are substituted is located inside the portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence.
13. The polynucleobase probe according to claim 4, wherein, in the portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence, at least one of the bases which become abasic or are substituted is located inside the portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence.
14. The polynucleobase probe according to claim 3, wherein, in the sequence complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence, a ratio of at least one of the bases which become abasic or are substituted with respect to any one of 3 to 5 guanines and cytosines is 1.
15. The polynucleobase probe according.sup.- to claim 4, wherein, in the sequence complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence, a ratio of at least one of the bases which become abasic or are substituted with respect to any one of 3 to 5 guanines and cytosines is 1.
16. The polynucleobase probe according to claim 5, wherein, in the sequence complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence, a ratio of at least one of the bases which become abasic or are substituted with respect to any one of 3 to 5 guanines and cytosines is 1.
17. The polynucleobase probe according to claim 2, wherein the target nucleic acid is a 10- to 50mer DNA or RNA.
18. The polynucleobase probe according to claim 17, wherein the target nucleic acid is a miRNA.
19. The polynucleobase probe according to claim 5 which is a DNA, RNA, LNA, GNA, BNA, or PNA.
20. The polynucleobase probe according to claim 6, which is a DNA, RNA, LNA, GNA, BNA, or PNA.
Description:
TECHNICAL FIELD
[0001] The present invention relates to a probe that can be utilized for nucleic acid detection with high specificity, a method for designing the same, and a method for detecting nucleic acid by utilizing the probe.
BACKGROUND ART
[0002] In recent years, small non-coding RNAs (ncRNAs) containing about 20 bases of microRNAs (miRNAs) have attracted attention because of their various functions. In particular, when these ncRNA levels correlate with diseases, ncRNAs can be utilized as markers.
[0003] When binding a target DNA or RNA to a probe by hybridization, a sequence of a binding part of a target DNA or RNA (hereinafter referred to as a "binding sequence") in which a large number of any one of guanine or cytosine having strong binding power is continuous, may be present in some case. In such a case, a phenomenon occurs in which false positives are likely to be generated due to a probe binding also to non-target DNAs or RNAs which have the same contiguous sequence as this sequence. In the related art, when a probe is bound to a long-chain target DNA or RNA which has such sequences that easily induce a false positive, a probe for a site that does not contain any sequence in which a large number of any one of guanine or cytosine is continuous was designed to be used. In general, it is perceived that a probe length of about 18-mer is necessary for detection of specific sequences by hybridization. However, in a case of detecting a target sequence composed of a short chain length of about 20-mer, such as an miRNA, it is not possible to design a probe that does not contain any sequence in which a large number of any one of guanine or cytosine is continuous, and therefore occurrence of false positives could not be avoided.
[0004] For this reason, as a method for detecting an ncRNA containing an miRNA, a method not based on detection of a specific sequence by hybridization, for example, a method utilizing polymerase chain reaction (PCR), oligonucleotide ligation assay (OLA), or ligase chain reaction (LCR) (Patent Document 1), and the like have been used.
[0005] In addition, as a method for improving specificity of miRNA measurement, a method using LNA with high affinity (Patent Document 2) is known. However, although this method increases binding power in hybridization, sequences in which a large number of any one of guanine or cytosine is continuous are generated, and therefore false positives could not be avoided.
[0006] Patent Document 3 discloses a method of irradiating a double-stranded oligonucleotide with light and detecting a SNP by using a difference in light absorption with use of a probe bound to a light-responsive organic group. The document discloses that any of a sequence in which an SNP site is not mutated and a sequence in which an SNP site is mutated can be used as a probe in the present document. In addition, Patent Document 3 discloses a probe in which a SNP site is substituted with a mutant as a probe for SNP. However, because the mutation is inserted in the SNP site in a target sequence itself to be bound, the sequences of these probes are designed as sequences complementary to the target sequence.
[0007] Peptide nucleic acid (PNA) is a DNA/RNA mimetic having a pseudopeptide skeleton in which N-(2-aminoethyl) glycine is bound by an amide bond instead of a sugar chain in DNA or RNA. PNA can be used as a new probe because it can form a double strand with DNA/RNA (Non-patent Document 1 and Non-patent Document 2).
[0008] Patent Document 4 discloses a method including a step of forming a double strand with PNA in which a part of bases is deleted and with nucleic acids; a step of reversibly binding by contacting a tagged base to a base-deleted portion (a portion where no pair is formed with a nucleic acid) of double-stranded PNA; and a step of detecting a target nucleic acid by detecting the tagged base. In this method, the label is attached to the tagged base rather than the PNA, and the target nucleic acid is detected by the binding of the tagged base to the PNA.
[0009] Non-Patent Document 3 discloses that a 15-mer DNA probe in which single base substitution, abasic site creation, or phenyl-substitution is performed has a lower Tm value, and thus lowers stability of the double strand as compared to a fully complementary probe. In particular, it has been reported that, in a case of a DNA and DNA double helix in which an abasic or phenyl-substituted DNA probe is used, a Tm value is reduced by about 40%, and therefore stability of the double helix is decreased. Non-Patent Document 4 discloses that, when a PNA and DNA double helix is formed, and a Tm value is measured by using an abasic or phenyl-substituted 15-mer PNA probe as above, the Tm value was 4.degree. C. for the case of abasic site creation, and the Tm value was 6.5.degree. C. for the case of phenyl substitution, which are a decrease in the Tm values, and therefore stability is decreased similarly to the DNA probe. In Non-patent document 5, one base of a 19-mer PNA probe is substituted with anthraquinone (AQ) having absorbance at 330 nm for the purpose of modifying the inside of a double helix structure. AQ has been shown to fit within the double strand while maintaining relatively high Tm values, whereas an abasic site has been shown to lower stability of double-strand formation.
RELATED DOCUMENT
Patent Document
[0010] [Patent Document 1] International Publication No. WO2005/098029
[0011] [Patent Document 2] International Publication No. WO2006/069584
[0012] [Patent Document 3] Japanese Unexamined Patent Publication No. 2001-346579
[0013] [Patent Document 4] International Publication No. WO2009/037473
Non-patent Document
[0014] [Non-patent document 1] Nielsen, P. E. et al., Science; 254: 1497-1500 (1991)
[0015] [Non-Patent Document 2] Michael Egholm, et al., Nature; 365: 566-568 (1993)
[0016] [Non-Patent Document 3] Millican, et al., Nucleic Acids Research; 12: 7435-7453 (1984)
[0017] [Non-patent document 4] Hemavathi Challa, et al., Tetrahedron Letters; 40: 8333-8336 (1999)
[0018] [Non-patent document 5] Bruce Armitage, et al., Nucleic Acids Research; 26: 715-720 (1998)
SUMMARY OF THE INVENTION
Technical Problem
[0019] An object of the present invention is to provide a means capable of detecting a target nucleic acid and a means capable of quantitatively determining a target nucleic acid with a low false positive rate (high specificity) through double-strand formation by hybridization of a probe and a target nucleic acid in detection of a short-chain target nucleic acid having a sequence in which any one of guanine or cytosine is continuous, without requiring complicated procedures such as ligation and amplification which have been employed in the related art. More specifically, an object of the present invention is to reduce a false positive rate in complementary strand formation by hybridization between a probe and a target nucleic acid in which one of guanine and cytosine has a contiguous sequence, so as to improve specificity. In particular, an object of the present invention is to provide a probe which is capable of reducing non-specific binding to a non-target nucleic acid in double-strand formation with a nucleic acid having a 10- to 50-mer target sequence having a sequence in which any one of guanine or cytosine is continuous, and thereby detecting or quantitatively determining a target nucleic acid with high specificity, which was difficult to perform with high specificity. As one example, the target nucleic acid is a miRNA having a sequence in which guanine or cytosine is continuous.
[0020] In general, making a sequence that is not complementary to a part of a target sequence by substituting a base of a probe or creating an abasic site reduces binding power to a target nucleic acid. It has been exceptionally reported that binding power is relatively maintained in an example in which one base of a PNA probe is substituted with a specific anthraquinone (AQ) such as 3,6-diaza (N.sup.3-Boc-aminoethyl) -4,7-dioxo-7-(2-anthraquinoyl)-hepta noic acid for labeling. However, a sequence that is not complementary to a part of a target sequence has not been adopted in the field of general nucleic acid detection and nucleic acid analysis, the sequence being obtained by substituting a base, creating an abasic site, or cleaving a sequence in a probe for detecting a nucleic acid by double-strand formation. In addition, there has been no concept of suppressing binding to a non-target sequence by substituting a base, creating an abasic site, or cleaving a sequence in a completely complementary probe. Furthermore, PNA has been known to stably form a double strand while being more sensitive to mismatches compared to DNA (described by Michael et al.).
Solution to Problem
[0021] The inventors of the present invention have attempted to design a probe via various approaches without being bound by such a common-sense idea in the field of genetic engineering. As a result, the inventors of the present invention have found that, when bases having strong binding power are continuous even in a case of a short-chain probe, binding power to non-target nucleic acids can be dramatically reduced while maintaining binding power to target nucleic acids by cleaving or substituting a part thereof or creating an abasic site. In addition, the inventors of the present invention have found that such a probe particularly has different binding power between a non-target nucleic acid and a target nucleic acid to the extent that false positives and positives can be distinguished in the detection of target nucleic acids in which bases (guanine and cytosine) with strong binding power are continuous. As a result, obtaining a probe useful for detecting target nucleic acids in which bases (guanine and cytosine) with strong binding power are continuous, and designing the same have been achieved. The present invention has been made based on such findings, and specifically relates to the following inventions.
[0022] (1) A polynucleobase probe including, in a sequence complementary to a target sequence having at least one sequence of any one of SEQ ID NOs: 1 to 10, a sequence in which at least one of bases in a portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence becomes abasic and/or is substituted; and/or a sequence which is cleaved to have, on an end, at least one sequence complementary to a sequence of 2 bases or less in any one sequence of SEQ ID NOs: 1 to 10 in the target sequence.
[0023] (2) The polynucleobase probe according to (1), which is 10- to 50-mer.
[0024] (3) The polynucleobase probe according to (2), which is 15- to 28-mer.
[0025] (4) The polynucleobase probe according to anyone of (1) to (3), to which a label is bound.
[0026] (5) The polynucleobase probe according to anyone of (1) to (4), in which, in the portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence, at least one of the bases which become abasic or are substituted is located inside the portion complementary to anyone sequence of SEQ ID NOs: 1 to 10 in the target sequence.
[0027] (6) The polynucleobase probe according to anyone of (1) to (5), in which, in the sequence complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence, a ratio of at least one of the bases which become abasic or are substituted with respect to any one of 3 to 5 guanines and cytosines is 1.
[0028] (7) The polynucleobase probe according to anyone of (1) to (6), in which the target nucleic acid is a 10- to 50-mer DNA or RNA.
[0029] (8) The polynucleobase probe according to (7), in which the target nucleic acid is a miRNA.
[0030] (9) The polynucleobase probe according to anyone of (1) to (8), which is a DNA, RNA, LNA, GNA, BNA, or PNA.
[0031] (10) A method for designing a polynucleobase probe sequence which is capable of binding to a target sequence having at least one sequence of any one of SEQ ID NOs: 1 to 10 with high specificity, the method including:
[0032] A) selecting a 10- to 50-mer sequence fully complementary to the target sequence as a fully complementary probe sequence; and
[0033] B) (i) in the fully complementary probe sequence, designing the polynucleobase probe sequence by substituting and/or making at least one of bases abasic in a portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in the target sequence, and/or
[0034] (ii) in the fully complementary probe sequence, designing the polynucleobase probe sequence by cleaving an end of the fully complementary probe sequence such that a portion complementary to anyone sequence of SEQ ID NOs: 1 to 10 in the target sequence becomes 2 bases or less.
[0035] (11) The method according to (10), in which the polynucleobase probe is 15- to 28-mer.
[0036] (12) The method according to (10) or (11), in which design of the polynucleobase probe sequence is performed by creating an abasic site, substituting, or cleaving such that a polynucleobase complementary to anyone sequence of SEQ ID NOs: 1 to 10 in the target sequence becomes 2 bases or less.
[0037] (13) A method for detecting a target nucleic acid having at least one sequence of any one of SEQ ID NOs: 1 to 10 in a test sample with high specificity, the method including:
[0038] preparing the test sample to detect the target nucleic acid;
[0039] bringing at least one kind of the polynucleobase probes according to any one of (1) to (9) in contact with the test sample; and
[0040] detecting the target nucleic acid bound to the polynucleobase probe.
[0041] (14) A method for quantitatively determining a target nucleic acid having at least one sequence of any one of SEQ ID NOs: 1 to 10 in a test sample with high specificity, the method including:
[0042] preparing the test sample to quantitatively determine the target nucleic acid;
[0043] contacting at least one kind of the polynucleobase probes according to any one of (1) to (9) with the test sample; and
[0044] quantitatively determining the target nucleic acid bound to the polynucleobase probe.
[0045] In the present specification, a "sequence in which any one of guanine or cytosine is continuous for 3 or more bases" or a "GC contiguous sequence" means the same as each other, and means GGGGGGG (SEQ ID NO: 1), CCCCCCC (SEQ ID NO: 2), GGGGGG (SEQ ID NO: 3), CCCCCC (SEQ ID NO: 4), GGGGG (SEQ ID NO: 5), CCCCC (SEQ ID NO: 6), GGGG (SEQ ID NO: 7), CCCC (SEQ ID NO: 8), GGG (SEQ ID NO: 9), and CCC (SEQ ID NO: 10). However, the term "GC contiguous sequence" in the words "substitution/abasic probe GC contiguous sequence" or "substituted/abasic probe GC contiguous sequence" means that a sequence before substitution/becoming abasic is a sequence in which any one of guanine or cytosine is continuous for 3 or more bases.
[0046] Because guanine and cytosine are complementary, a probe complementary thereto also has a GC contiguous sequence in a case where a target nucleic acid has a GC contiguous sequence. In the present specification, the term "GC contiguous sequence" is used both when the sequence is present in a target nucleic acid and when the sequence is present in a probe. In particular, a GC contiguous sequence present in a target nucleic acid/sequence is referred to as a "sequence of any one of SEQ ID NOs: 1 to 10 in a target nucleic acid/sequence" or a "target GC contiguous sequence". In addition, a GC contiguous sequence complementary to the target GC contiguous sequence present in the probe, in particular, a GC contiguous sequence which is complementary to a target GC contiguous sequence and is present in the probe fully complementary to a target sequence before cleavage, abasic site creation, or substitution, is referred to as a "probe GC contiguous sequence" or a "sequence portion complementary to any one sequence of SEQ ID NOs: 1 to 10 in a target sequence". Such a probe sequence that is fully complementary to a target sequence before cleavage, abasic site creation, or substitution may be referred to as a "fully complementary probe sequence". On the other hand, a probe sequence in which guanine or cytosine in the probe GC contiguous sequence becomes abasic or is substituted is referred to as a "substituted/abasic probe sequence". A sequence corresponding to a probe GC contiguous sequence in the substituted/abasic probe sequence is referred to as a "substituted/abasic probe GC contiguous sequence". For example, the probe of FIG. 1A shows a probe GC contiguous sequence in a fully complementary probe sequence, and the probe of FIG. 1B shows a substituted/abasic probe GC contiguous sequence in a substituted/abasic probe sequence.
[0047] In the present invention, the term "nucleobase" includes nucleotide analogs in addition to naturally occurring nucleotides. Naturally occurring nucleotides are deoxyribonucleotides or ribonucleotides having bases of adenine (A), guanine (G), cytosine (C), thymine (T), and/or uracil (U). Nucleotide analogues mean artificial nucleotides or nucleotide mimetics which have the same base as the naturally occurring deoxyribonucleotide or ribonucleotide described above, but in which a ribose chemical structure and/or a phosphodiester bond chemical structure is artificially modified. Examples thereof include glycol nucleic acid (GNA), bridged nucleic acid (BNA), 2',4'-locked nucleic acid (LNA), peptide nucleic acid (PNA), threose nucleic acid (TNA), and morpholino nucleic acids. In the present specification, GNA, BNA, LNA, PNA, TNA, and morpholino nucleic acids may be interpreted as monomers or as polymers depending on context.
[0048] In the present invention, the term "polynucleobase" means a polymer compound in which the above-mentioned nucleobase is linearly polymerized. The polynucleobase may be a homopolymer composed of only one type of nucleobase (such as only a naturally occurring polynucleotide, or only a constituent unit of PNA). In addition, the polynucleobase may also be a copolymer of two or more types of nucleobases (such as a naturally occurring polynucleotide and PNA, or BNA and LNA). Accordingly, polynucleotides such as DNA and RNA, and polymers of GNA, BNA, LNA, PNA, TNA, and morpholino nucleic acids are also included in the polynucleobase. In the present specification, the polynucleobase may contain a pyrrole-imidazole polyamide (Peter B. Dervan et. Al., Nature (1998) 391-468; P. B. Dervan and R. W. Burli, Current Opinion in Chemical Biology 3 (1999) 688-693; P. B. Dervan, Bioorganic & Medicinal Chemistry 9 (2001) 215-2235.). In this case, abase in the present specification can be substituted with pyrrole and/or imidazole.
[0049] In the present specification, a "probe" and a "polynucleobase probe" are the same meaning, and mean a polynucleobase used to form a double strand by hybridization with a target sequence. The polynucleobase probe of the present invention includes a sequence in which at least one base in a probe GC contiguous sequence in a fully complementary probe sequence becomes abasic or is substituted (substituted/abasic probe sequence), or a sequence in which all bases from at least one base in the probe GC contiguous sequence to one end of a fully complementary probe are cleaved, as a portion that binds to a target sequence based on a fully complementary probe sequence complementary to a target sequence having at least one target GC contiguous sequence. In the present specification, the term "cleavage" means that a probe is designed such that only 2 or less bases of amino acids constituting the probe GC contiguous sequence are left at the end of the probe in the design stage of the probe. It is not necessary to perform "cleavage" in an actual production process of the probe. Accordingly, a "sequence cleaved to have, at the end, at least one sequence complementary to a sequence of 2 bases or less in any one sequence of SEQ ID NOs: 1 to 10 in the target sequence" means a sequence in which remaining bases excluding 2 or less bases located at the one end of a "probe GC contiguous sequence portion" contained in the fully complementary probe, and all bases up to one end of a "fully complementary probe" which are adjacent to the remaining bases are missing, or a sequence that contains, at the end of the probe, 2 or less bases derived from the end of the probe GC contiguous sequence portion.
[0050] When two or more target GC contiguous sequences are present in a target sequence, cleavage, substitution, or abasic site creation at a probe may be performed in any one of the probe GC contiguous sequences, or may be performed in two or more probe GC contiguous sequences. Preferably, the probe of the present invention is cleaved or substituted, or becomes abasic in the probe GC contiguous sequences at all locations. For example, when two or more target GC contiguous sequences are present in the target sequence, the probe of the present invention may be cleaved in any one of the probe GC contiguous sequences, and may be substituted or become abasic in the other probe GC contiguous sequence. Alternatively, when two or more target GC contiguous sequences are present in the target sequence, the probe of the present invention may be cleaved at two probe GC contiguous sequences, and when another probe GC contiguous sequence is present, the probe of the present invention may be substituted or become abasic at the probe GC contiguous sequence. Alternatively, when two or more target GC contiguous sequences are present in the target sequence, the probe of the present invention maybe substituted or become abasic in probe GC contiguous sequences at all locations. In other words, only one of cleavage, substitution, and abasic site creation may be used in probe GC contiguous sequences at all locations, or any one of cleavage, substitution, and abasic site creation is used for each of a plurality of probe GC contiguous sequences present in one probe so that cleavage, substitution, and abasic site creation are used in combination in one probe as a result. Furthermore, cleavage, substitution, and abasic site creation may be used in combination in one probe GC contiguous sequence. The probe of the present invention preferably does not have a probe GC contiguous sequence as a result of cleavage, substitution, or abasic site creation in probe GC contiguous sequences at all locations in an initially selected fully complementary probe sequence.
[0051] Furthermore, the probe or the polynucleobase probe of the present invention may have a portion that does not bind to a target sequence in addition to the above-described portion that binds to the target sequence. Such a portion that does not bind to the target sequence may be a label or a linker, maybe bound to another molecule, or maybe used for the purpose of improving stability. For example, such a portion that does not bind to the target sequence may contain a polynucleobase that is not complementary to the target sequence such as a tag sequence or a linker sequence, or may be bound a low molecular weight compound or proteins. In one example, a portion that does not bind to the target sequence is "modification" to be described later.
[0052] In the present specification, the phrase "becoming abasic" means that no base portion is present in a nucleobase. In an abasic site of DNA or RNA, no base is bound to the 1' position of the sugar, but a hydroxyl group, a hydrogen atom, a lower acyl group (such as an acetyl group), or a lower alkyl group (such as a methyl group) is bound thereto. In a case of an abasic site of PNA, a substituent of a methyl carbonyl group bound to tertiary amine of a glycine skeleton is a hydroxyl group, a hydrogen atom, a lower acyl group (such as an acetyl group), or a lower alkyl group (such as a methyl group) instead of a base. Alternatively, in the case of an abasic site of PNA, a nitrogen atom of a glycine skeleton is substituted with a carbon atom (which may have a lower acyl group (such as an acetyl group) or a lower alkyl group (such as a methyl group) as a substituent).
[0053] In addition, in the present specification, a case in which a base is "substituted" includes a case in which a base portion in a nucleobase is substituted with a non-complementary base. In addition, a case in which a base in a probe sequence is "substituted" includes a case in which a base portion in a nucleobase is substituted with a group other than adenine, guanine, cytosine, uracil, and thymine (for example, a phenyl group, an anthraquinone group, and the like). A group introduced by base substitution is preferably a group that does not inhibit double-strand formation with a target sequence by another non-substituted base in the probe sequence.
[0054] A position of a base to become abasic or be substituted in the probe GC contiguous sequence is not particularly limited. For example, a base may be in the inside of the probe GC contiguous sequence (such as G*G and C*CC. Herein, "*" represents a base to become abasic or be substituted. The same applies in the present specification), or at the end (such as GG * and *CC). Preferably, guanine or cytosine in the middle of the inside of the probe GC contiguous sequence becomes abasic or is substituted (such as C*C and GG*GG). For example, in a case where the probe GC contiguous sequence is GGG, G*G is preferable, and similarly, in a case of CCC, C*C is preferable. In addition, preferably, the GC contiguous sequence after substitution or becoming abasic does not have a sequence in which G or C is continuous for 3 or more bases.
[0055] The number of bases to become abasic or be substituted in the probe GC contiguous sequence is not particularly limited as long as binding power with a target sequence is maintained. For example, a ratio may be 2 or 3 bases to 6 to 7 guanines or cytosines, 1 or 2 bases to 3 to 5 guanines or cytosines, 1 base to 3 to 4 guanines or cytosines, or 1 base to 3 guanines or cytosines.
[0056] Examples of substituted/abasic probe GC contiguous sequences include G*GG*GG (SEQ ID NO: 11), GG*G*GG (SEQ ID NO: 12), GG*GG*G (SEQ ID NO: 13), *G*G*GG (SEQ ID NO: 14), *G*GG*G (SEQ ID NO: 15), *GG*G*G (SEQ ID NO: 16), *GG*GG* (SEQ ID NO: 17), G*G*G*G (SEQ ID NO: 18), G*GG*G* (SEQ ID NO: 19), G*G*GG* (SEQ ID NO: 20), GG*G*G* (SEQ ID NO: 21), C*CC*CC (SEQ ID NO: 22), CC*C*CC (SEQ ID NO: 23), CC*CC*C (SEQ ID NO: 24), *C*C*CC (SEQ ID NO: 25), *C*CC*C (SEQ ID NO: 26), *CC*C*C (SEQ ID NO: 27), *CC*CC* (SEQ ID NO 28), C*C*C*C (SEQ ID NO 29), C*C*CC* (SEQ ID NO: 30), C*CC*C* (SEQ ID NO: 31), CC*C*C* (SEQ ID NO: 32), *GG*GG (SEQ ID NO: 33), G*G*GG (SEQ ID NO: 34), G*GG*G (SEQ ID NO: 35), GG*G*G (SEQ ID NO: 36), GG*GG* (SEQ ID NO: 37), *G*G*G (SEQ ID NO: 38), *G*GG* (SEQ ID NO: 39), *GG*G* (SEQ ID NO: 40), G*G*G* (SEQ ID NO: 41), *CC*CC (SEQ ID NO: 42), C*C*CC (SEQ ID NO: 43), C*CC*C (SEQ ID NO: 44), CC*C*C (SEQ ID NO: 45), CC*CC* (SEQ ID NO: 46), *C*C*C (SEQ ID NO: 47), *C*CC* (SEQ ID NO: 48), *CC*C* (SEQ ID NO: 49), C*C*C* (SEQ ID NO: 50), GG*GG (SEQ ID NO: 51), *G*GG (SEQ ID NO: 52), *GG*G (SEQ ID NO: 53), G*G*G (SEQ ID NO: 54), G*GG* (SEQ ID NO: 55), GG*G* (SEQ ID NO: 56), CC*CC (SEQ ID NO: 57), *C*CC (SEQ ID NO: 58), *CC*C (SEQ ID NO: 59), C*C*C (SEQ ID NO: 60), C*CC* (SEQ ID NO: 61), CC*C* (SEQ ID NO: 62), G*GG (SEQ ID NO: 63), GG*G (SEQ ID NO: 64), *G*G (SEQ ID NO: 65), *GG* (SEQ ID NO: 66), G*G* (SEQ ID NO: 67), C*CC (SEQ ID NO: 68), CC*C (SEQ ID NO: 69), *C*C (SEQ ID NO: 70), *CC* (SEQ ID NO: 71), C*C* (SEQ ID NO: 72), *GG (SEQ ID NO: 73), G*G (SEQ ID NO: 74), GG* (SEQ ID NO: 75), *G* (SEQ ID NO: 76), *CC (SEQ ID NO: 77), C*C (SEQ ID NO: 78), CC* (SEQ ID NO: 79), and *C* (SEQ ID NO: 80).
[0057] In the polynucleobase probe of the present invention, a chain length of a portion binding to a target sequence is a length such that a binding rate (a false positive rate) with a nucleic acid having a sequence other than a target sequence is increased due to the presence of a probe GC contiguous sequence, and is specifically is 10- to 50-mer. For example, a chain length of a portion binding to a target sequence in the polynucleobase probe of the present invention can be 10-mer or more, 11-mer or more, 12-mer or more, 13-mer or more, 14-mer or more, 15-mer or more, 16-mer or more, 17-mer or more, or 18-mer or more.
[0058] In addition, a chain length of a portion binding to a target sequence in the polynucleobase probe of the present invention can be 50-mer or less, 45-mer or less, 40-mer or less, 35-mer or less, 30-mer or less, 29-mer or less, 28-mer or less, 27-mer or less, 26-mer or less, or 25-mer or less.
[0059] For example, a chain length of a portion binding to a target sequence in the polynucleobase probe of the present invention can be 10- to 40-mer, 13- to 30-mer, 15- to 28-mer, or 18- to 25-mer.
[0060] The above-mentioned "chain length of a portion binding to a target sequence in the polynucleobase probe of the present invention" may be read as a chain length of the polynucleobase probe.
[0061] The nucleobase probe in the present specification may be appropriately "modified". For example, the modification includes a label for detection, a functional group for binding, and the like. Any label can be used without particular limitation as long as it can be used in the field of nucleic acid detection. For example, various methods such as radioactive substance (RI), enzyme (biotin and the like), hapten (digoxigenin (DIG) and the like), affinity tag, and fluorescent colorants are known.
[0062] As fluorescent colorants, various types of red, orange, yellow, green, blue, and purple are known. It is possible to use dansyl, TRITC, fluorescein, rhodamine, Texas red, IAEDANS, cyanine dyes (Cy3, Cy3.5, Cy5, Cy5.5, Cy7), Hoechst, BFP, CFP, WGFP, GFP, YFP, RFP, EGFP, FITC, AlexaFluor, tdTomato, TRITC, TXRED, mCherry-A, mCherry-C, and the like.
[0063] In addition, the probe of the present invention may be immobilized on a solid phase. For example, the probe may be bound to an array, a bead, or a chip.
[0064] A "functional group for binding" is not particularly limited as long as it is a group used for binding the nucleobase probe in the present specification to a solid phase or another substance, and examples thereof include a hydroxyl group, a halogen atom, an amino group, an amido group, an imide group, a guanidine group, a urea group, an alkene, an alkyne, a sulfonic acid, a carboxylic acid group, an ester group, and the like.
[0065] The term "target nucleic acid" in the present specification means a nucleic acid having a GC contiguous sequence, which is a target nucleic acid of which the presence is to be detected or quantitatively determined by the probe of the present invention. For example, in a case where the probe of the present invention is used for the purpose of diagnosing a disease or disorder, a target nucleic acid means DNA or RNA derived from a living body. A target nucleic acid may have 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 GC contiguous sequence.
[0066] A length of the target nucleic acid is not particularly limited, but a target nucleic acid of 50-mer or less, 45-mer or less, 40-mer or less, 35-mer or less, 30-mer or less, 29-mer or less, 28-mer or less, 27-mer or less, 26-mer or less, or 25-mer or less are preferable from the viewpoint of the probe of the present invention being particularly effective for double-strand formation with a target nucleic acid for which a probe avoiding a target GC contiguous sequence cannot be designed. For example, a chain length of the target nucleic acid can be 10-mer or more, 11-mer or more, 12-mer or more, 13-mer or more, 14-mer or more, 15-mer or more, 16-mer or more, 17-mer or more, or 18-mer or more. As an example, a chain length of the target nucleic acid is 10- to 50-mer, 10- to 40-mer, 13- to 30-mer, 15- to 28-mer, or 18- to 25-mer.
[0067] A representative example of target nucleic acids includes an miRNA having a GC contiguous sequence. Examples of such sequences include sequences described in the following table. In the table, the underline indicates a GC contiguous sequence. The numerical values beside the sequence represent, in order, a full length of the sequence, the number of target GC contiguous sequences contained in the target nucleic acid, and a length of the longest target GC contiguous sequence contained in the target nucleic acid.
[0068] Examples of target sequences having GC contiguous sequences or sequences complementary to the target sequences or miRNAs are as follows:
TABLE-US-00001 hsa-miR-3676-5p: (SEQ ID NO: 81) AGGAGAUCCUGGGUU, hsa-miR-4279: (SEQ ID NO: 82) CUCUCCUCCCGGCUUC, hsa-miR-4310: (SEQ ID NO: 83) GCAGCAUUCAUGUCCC, hsa-miR-4261: (SEQ ID NO: 84) AGGAAACAGGGACCCA, hsa-miR-1281: (SEQ ID NO: 85) UCGCCUCCUCCUCUCCC, hsa-miR-3201: (SEQ ID NO: 86) GGGAUAUGAAGAAAAAU, hsa-miR-4251: (SEQ ID NO: 87) CCUGAGAAAAGGGCCAA, hsa-miR-4296: (SEQ ID NO: 88) AUGUGGGCUCAGGCUCA, hsa-miR-4304: (SEQ ID NO: 89) CCGGCAUGUCCAGGGCA, hsa-miR-4317: (SEQ ID NO: 90) ACAUUGCCAGGGAGUUU, hsa-miR-4318: (SEQ ID NO: 91) CACUGUGGGUACAUGCU, hsa-miR-4319: (SEQ ID NO: 92) UCCCUGAGCAAAGCCAC, hsa-miR-4328: (SEQ ID NO: 93) CCAGUUUUCCCAGGAUU, hsa-miR-4419a: (SEQ ID NO: 94) UGAGGGAGGAGACUGCA, hsa-miR-4441: (SEQ ID NO: 95) ACAGGGAGGAGAUUGUA, hsa-miR-4442: (SEQ ID NO: 96) GCCGGACAAGAGGGAGG, hsa-miR-4443: (SEQ ID NO: 97) UUGGAGGCGUGGGUUUU, hsa-miR-4455: (SEQ ID NO: 98) AGGGUGUGUGUGUUUUU, hsa-miR-4481: (SEQ ID NO: 99) GGAGUGGGCUGGUGGUU, hsa-miR-4486: (SEQ ID NO: 100) GCUGGGCGAGGCUGGCA, hsa-miR-4499: (SEQ ID NO: 101) AAGACUGAGAGGAGGGA, hsa-miR-4535: (SEQ ID NO: 102) GUGGACCUGGCUGGGAC, hsa-miR-1274b: (SEQ ID NO: 103) UCCCUGUUCGGGCGCCA, hsa-miR-1280: (SEQ ID NO: 104) UCCCACCGCUGCCACCC, hsa-miR-4294: (SEQ ID NO: 105) GGGAGUCUACAGCAGGG, hsa-miR-4497: (SEQ ID NO: 106) CUCCGGGACGGCUGGGC, hsa-miR-3195: (SEQ ID NO: 107) CGCGCCGGGCCCGGGUU, hsa-miR-1207-3p: (SEQ ID NO: 108) UCAGCUGGCCCUCAUUUC, hsa-miR-1260: (SEQ ID NO: 109) AUCCCACCUCUGCCACCA, hsa-miR-1274a: (SEQ ID NO: 110) GUCCCUGUUCAGGCGCCA, hsa-miR-1308: (SEQ ID NO: 111) GCAUGGGUGGUUCAGUGG, hsa-miR-1321: (SEQ ID NO: 112) CAGGGAGGUGAAUGUGAU, hsa-miR-1825: (SEQ ID NO: 113) UCCAGUGCCCUCCUCUCC, hsa-miR-3155b: (SEQ ID NO: 114) CCAGGCUCUGCAGUGGGA, hsa-miR-4300: (SEQ ID NO: 115) UGGGAGCUGGACUACUUC, hsa-miR-4308: (SEQ ID NO: 116) UCCCUGGAGUUUCUUCUU, hsa-miR-4320: (SEQ ID NO: 117) GGGAUUCUGUAGCUUCCU, hsa-miR-4519: (SEQ ID NO: 118) CAGCAGUGCGCAGGGCUG, hsa-miR-5587-5p: (SEQ ID NO: 119) AUGGUCACCUCCGGGACU, hsa-miR-5703: (SEQ ID NO: 120) AGGAGAAGUCGGGAAGGU, hsa-miR-6126: (SEQ ID NO: 121) GUGAAGGCCCGGCGGAGA, mmu-miR-696: (SEQ ID NO: 122) GCGUGUGCUUGCUGUGGG, hsa-miR-4314: (SEQ ID NO: 123) CUCUGGGAAAUGGGACAG, hsa-miR-4505: (SEQ ID NO: 124) AGGCUGGGCUGGGACGGA, hsa-miR-4530: (SEQ ID NO: 125) CCCAGCAGGACGGGAGCG, hsa-miR-4710: (SEQ ID NO: 126) GGGUGAGGGCAGGUGGUU, hsa-miR-4417: (SEQ ID NO: 127) GGUGGGCUUCCCGGAGGG, hsa-miR-1224-5p: (SEQ ID NO: 128) GUGAGGACUCGGGAGGUGG, hsa-miR-1290: (SEQ ID NO: 129) UGGAUUUUUGGAUCAGGGA, hsa-miR-3176: (SEQ ID NO: 130) ACUGGCCUGGGACUACCGG, hsa-miR-3649: (SEQ ID NO: 131) AGGGACCUGAGUGUCUAAG, hsa-miR-4289: (SEQ ID NO: 132) GCAUUGUGCAGGGCUAUCA, hsa-miR-4329: (SEQ ID NO: 133) CCUGAGACCCUAGUUCCAC, hsa-miR-4487: (SEQ ID NO: 134) AGAGCUGGCUGAAGGGCAG, hsa-miR-4736: (SEQ ID NO: 135) AGGCAGGUUAUCUGGGCUG, hsa-miR-5588-3p: (SEQ ID NO: 136) AAGUCCCACUAAUGCCAGC, hsa-miR-585: (SEQ ID NO: 137) UGGGCGUAUCUGUAUGCUA, hsa-miR-6070: (SEQ ID NO: 138) CCGGUUCCAGUCCCUGGAG, hsa-miR-6130: (SEQ ID NO: 139) UGAGGGAGUGGAUUGUAUG, hsa-miR-6131: (SEQ ID NO: 140) GGCUGGUCAGAUGGGAGUG, hsa-miR-632: (SEQ ID NO: 141) GUGUCUGCUUCCUGUGGGA, hsa-miR-648: (SEQ ID NO: 142) AAGUGUGCAGGGCACUGGU, mmu-miR-684: (SEQ ID NO: 143)
AGUUUUCCCUUCAAGUCAA, mmu-miR-698: (SEQ ID NO: 144) CAUUCUCGUUUCCUUCCCU, hsa-miR-3141: (SEQ ID NO: 145) GAGGGCGGGUGGAGGAGGA, hsa-miR-3181: (SEQ ID NO: 146) AUCGGGCCCUCGGCGCCGG, hsa-miR-4265: (SEQ ID NO: 147) CUGUGGGCUCAGCUCUGGG, hsa-miR-4287: (SEQ ID NO: 148) UCUCCCUUGAGGGCACUUU, hsa-miR-4290: (SEQ ID NO: 149) UGCCCUCCUUUCUUCCCUC, hsa-miR-6080: (SEQ ID NO: 150) UCUAGUGCGGGCGUUCCCG, hsa-miR-6129: (SEQ ID NO: 151) UGAGGGAGUUGGGUGUAUA, hsa-miR-6133: (SEQ ID NO: 152) UGAGGGAGGAGGUUGGGUA, hsa-miR-6127: (SEQ ID NO: 153) UGAGGGAGUGGGUGGGAGG, rno-miR-347: (SEQ ID NO: 154) UGUCCCUCUGGGUCGCCCA, hsa-miR-1205: (SEQ ID NO: 155) UCUGCAGGGUUUGCUUUGAG, hsa-miR-1231: (SEQ ID NO: 156) GUGUCUGGGCGGACAGCUGC, hsa-miR-1276: (SEQ ID NO: 157) UAAAGAGCCCUGUGGAGACA, hsa-miR-1976: (SEQ ID NO: 158) CCUCCUGCCCUCCUUGCUGU, hsa-miR-3115: (SEQ ID NO: 159) AUAUGGGUUUACUAGUUGGU, hsa-miR-3622b-5p: (SEQ ID NO: 160) AGGCAUGGGAGGUCAGGUGA, hsa-miR-3917: (SEQ ID NO: 161) GCUCGGACUGAGCAGGUGGG, hsa-miR-4301: (SEQ ID NO: 162) UCCCACUACUUCACUUGUGA, hsa-miR-4326: (SEQ ID NO: 163) UGUUCCUCUGUCUCCCAGAC, hsa-miR-4429: (SEQ ID NO: 164) AAAAGCUGGGCUGAGAGGCG, hsa-miR-4485: (SEQ ID NO: 165) UAACGGCCGCGGUACCCUAA, hsa-miR-4506: (SEQ ID NO: 166) AAAUGGGUGGUCUGAGGCAA, hsa-miR-4784: (SEQ ID NO: 167) UGAGGAGAUGCUGGGACUGA, hsa-miR-490-5p: (SEQ ID NO: 168) CCAUGGAUCUCCAGGUGGGU, hsa-miR-572: (SEQ ID NO: 169) GUCCGCUCGGCGGUGGCCCA, hsa-miR-591: (SEQ ID NO: 170) AGACCAUGGGUUCUCAUUGU, hsa-miR-6083: (SEQ ID NO: 171) CUUAUAUCAGAGGCUGUGGG, hsa-miR-609: (SEQ ID NO: 172) AGGGUGUUUCUCUCAUCUCU, hsa-miR-6722-5p: (SEQ ID NO: 173) AGGCGCACCCGACCACAUGC, hsa-miR-877: (SEQ ID NO: 174) GUAGAGGAGAUGGCGCAGGG, mmu-miR-805: (SEQ ID NO: 175) GAAUUGAUCAGGACAUAGGG, hsa-miR-1233: (SEQ ID NO: 176) UGAGCCCUGUCCUCCCGCAG, hsa-miR-202: (SEQ ID NO: 177) AGAGGUAUAGGGCAUGGGAA, hsa-miR-326: (SEQ ID NO: 178) CCUCUGGGCCCUUCCUCCAG, hsa-miR-4324: (SEQ ID NO: 179) CCCUGAGACCCUAACCUUAA, hsa-miR-4648: (SEQ ID NO: 180) UGUGGGACUGCAAAUGGGAG, hsa-miR-4701-3p: (SEQ ID NO: 181) AUGGGUGAUGGGUGUGGUGU, hsa-miR-6086: (SEQ ID NO: 182) GGAGGUUGGGAAGGGCAGAG, mmu-miR-343: (SEQ ID NO: 183) UCUCCCUUCAUGUGCCCAGA, hsa-miR-4507: (SEQ ID NO: 184) CUGGGUUGGGCUGGGCUGGG, gga-miR-757: (SEQ ID NO: 185) GCAGAGCUGCAGAUGGGAUUC, hsa-miR-1178: (SEQ ID NO: 186) UUGCUCACUGUUCUUCCCUAG, hsa-miR-1181: (SEQ ID NO: 187) CCGUCGCCGCCACCCGAGCCG, hsa-miR-1185: (SEQ ID NO: 188) AGAGGAUACCCUUUGUAUGUU, hsa-miR-1203: (SEQ ID NO: 189) CCCGGAGCCAGGAUGCAGCUC, hsa-miR-1257: (SEQ ID NO: 190) AGUGAAUGAUGGGUUCUGACC, hsa-miR-1286: (SEQ ID NO: 191) UGCAGGACCAAGAUGAGCCCU, hsa-miR-1288: (SEQ ID NO: 192) UGGACUGCCCUGAUCUGGAGA, hsa-miR-1295: (SEQ ID NO: 193) UUAGGCCGCAGAUCUGGGUGA, hsa-miR-129-5p: (SEQ ID NO: 194) CUUUUUGCGGUCUGGGCUUGC, hsa-miR-1302: (SEQ ID NO: 195) UUGGGACAUACUUAUGCUAAA, hsa-miR-1302: (SEQ ID NO: 196) UUGGGACAUACUUAUGCUAAA, hsa-miR-1302: (SEQ ID NO: 197) UUGGGACAUACUUAUGCUAAA, hsa-miR-1302: (SEQ ID NO: 198) UUGGGACAUACUUAUGCUAAA, hsa-miR-1302: (SEQ ID NO: 199) UUGGGACAUACUUAUGCUAAA, hsa-miR-130b*: (SEQ ID NO: 200) ACUCUUUCCCUGUUGCACUAC, hsa-miR-140-3p: (SEQ ID NO: 201) UACCACAGGGUAGAACCACGG, hsa-miR-1909*: (SEQ ID NO: 202) UGAGUGCCGGUGCCUGCCCUG, hsa-miR-190b: (SEQ ID NO: 203) UGAUAUGUUUGAUAUUGGGUU, hsa-miR-21*: (SEQ ID NO: 204) CAACACCAGUCGAUGGGCUGU, hsa-miR-2114*: (SEQ ID NO: 205) CGAGCCUCAAGCAAGGGACUU, hsa-miR-222:
(SEQ ID NO: 206) AGCUACAUCUGGCUACUGGGU, hsa-miR-2277-3p: (SEQ ID NO: 207) UGACAGCGCCCUGCCUGGCUC, hsa-miR-23a: (SEQ ID NO: 208) AUCACAUUGCCAGGGAUUUCC, hsa-miR-23b: (SEQ ID NO: 209) AUCACAUUGCCAGGGAUUACC, hsa-miR-25*: (SEQ ID NO: 210) AGGCGGAGACUUGGGCAAUUG, hsa-miR-2909: (SEQ ID NO: 211) GUUAGGGCCAACAUCUCUUGG, hsa-miR-3124-5p: (SEQ ID NO: 212) UUCGCGGGCGAAGGCAAAGUC, hsa-miR-3130-3p: (SEQ ID NO: 213) GCUGCACCGGAGACUGGGUAA, hsa-miR-3130-5p: (SEQ ID NO: 214) UACCCAGUCUCCGGUGCAGCC, hsa-miR-3155a: (SEQ ID NO: 215) CCAGGCUCUGCAGUGGGAACU, hsa-miR-3156-3p: (SEQ ID NO: 216) CUCCCACUUCCAGAUCUUUCU, hsa-miR-3158-5p: (SEQ ID NO: 217) CCUGCAGAGAGGAAGCCCUUC, hsa-miR-3194-5p: (SEQ ID NO: 218) GGCCAGCCACCAGGAGGGCUG, hsa-miR-3622b-3p: (SEQ ID NO: 219) UCACCUGAGCUCCCGUGCCUG, hsa-miR-3657: (SEQ ID NO: 220) UGUGUCCCAUUAUUGGUGAUU, hsa-miR-3659: (SEQ ID NO: 221) UGAGUGUUGUCUACGAGGGCA, hsa-miR-3918: (SEQ ID NO: 222) ACAGGGCCGCAGAUGGAGACU, hsa-miR-4269: (SEQ ID NO: 223) GCAGGCACAGACAGCCCUGGC, hsa-miR-4321: (SEQ ID NO: 224) UUAGCGGUGGACCGCCCUGCG, hsa-miR-4422: (SEQ ID NO: 225) AAAAGCAUCAGGAAGUACCCA, hsa-miR-4523: (SEQ ID NO: 226) GACCGAGAGGGCCUCGGCUGU, hsa-miR-4529-3p: (SEQ ID NO: 227) AUUGGACUGCUGAUGGCCCGU, hsa-miR-455-3p: (SEQ ID NO: 228) GCAGUCCAUGGGCAUAUACAC, hsa-miR-4635: (SEQ ID NO: 229) UCUUGAAGUCAGAACCCGCAA, hsa-miR-4690-3p: (SEQ ID NO: 230) GCAGCCCAGCUGAGGCCUCUG, hsa-miR-4717-3p: (SEQ ID NO: 231) ACACAUGGGUGGCUGUGGCCU, hsa-miR-4732-3p: (SEQ ID NO: 232) GCCCUGACCUGUCCUGUUCUG, hsa-miR-4746-3p: (SEQ ID NO: 233) AGCGGUGCUCCUGCGGGCCGA, hsa-miR-4761-3p: (SEQ ID NO: 234) GAGGGCAUGCGCACUUUGUCC, hsa-miR-4804-3p: (SEQ ID NO: 235) UGCUUAACCUUGCCCUCGAAA, hsa-miR-483-3p: (SEQ ID NO: 236) UCACUCCUCUCCUCCCGUCUU, hsa-miR-488*: (SEQ ID NO: 237) CCCAGAUAAUGGCACUCUCAA, hsa-miR-5006-3p: (SEQ ID NO: 238) UUUCCCUUUCCAUCCUGGCAG, hsa-miR-5006-5p: (SEQ ID NO: 239) UUGCCAGGGCAGGAGGUGGAA, hsa-miR-502-5p: (SEQ ID NO: 240) AUCCUUGCUAUCUGGGUGCUA, hsa-miR-506: (SEQ ID NO: 241) UAAGGCACCCUUCUGAGUAGA, hsa-miR-5089-5p: (SEQ ID NO: 242) GUGGGAUUUCUGAGUAGCAUC, hsa-miR-5571-5p: (SEQ ID NO: 243) CAAUUCUCAAAGGAGCCUCCC, hsa-miR-5588-5p: (SEQ ID NO: 244) ACUGGCAUUAGUGGGACUUUU, hsa-miR-5589-5p: (SEQ ID NO: 245) GGCUGGGUGCUCUUGUGCAGU, hsa-miR-5694: (SEQ ID NO: 246) CAGAUCAUGGGACUGUCUCAG, hsa-miR-583: (SEQ ID NO: 247) CAAAGAGGAAGGUCCCAUUAC, hsa-miR-588: (SEQ ID NO: 248) UUGGCCACAAUGGGUUAGAAC, hsa-miR-6075: (SEQ ID NO: 249) ACGGCCCAGGCGGCAUUGGUG, hsa-miR-6077: (SEQ ID NO: 250) GGGAAGAGCUGUACGGCCUUC, hsa-miR-610: (SEQ ID NO: 251) UGAGCUAAAUGUGUGCUGGGA, hsa-miR-631: (SEQ ID NO: 252) AGACCUGGCCCAGACCUCAGC, hsa-miR-6500-3p: (SEQ ID NO: 253) ACACUUGUUGGGAUGACCUGC, hsa-miR-6503-3p: (SEQ ID NO: 254) GGGACUAGGAUGCAGACCUCC, hsa-miR-6507-5p: (SEQ ID NO: 255) GAAGAAUAGGAGGGACUUUGU, hsa-miR-6508-5p: (SEQ ID NO: 256) UCUAGAAAUGCAUGACCCACC, hsa-miR-6513-3p: (SEQ ID NO: 257) UCAAGUGUCAUCUGUCCCUAG, hsa-miR-6515-5p: (SEQ ID NO: 258) UUGGAGGGUGUGGAAGACAUC, hsa-miR-652: (SEQ ID NO: 259) AAUGGCGCCACUAGGGUUGUG, hsa-miR-671-3p: (SEQ ID NO: 260) UCCGGUUCUCAGGGCUCCACC, hsa-miR-6718-5p: (SEQ ID NO: 261) UAGUGGUCAGAGGGCUUAUGA, mmu-miR-700: (SEQ ID NO: 262) CACGCGGGAACCGAGUCCACC, mmu-miR-714: (SEQ ID NO: 263) CGACGAGGGCCGGUCGGUCGC, rno-miR-336: (SEQ ID NO: 264) UCACCCUUCCAUAUCUAGUCU, hsa-miR-1539: (SEQ ID NO: 265) UCCUGCGCGUCCCAGAUGCCC, hsa-miR-188-3p: (SEQ ID NO: 266) CUCCCACAUGCAGGGUUUGCA, hsa-miR-188-5p: (SEQ ID NO: 267) CAUCCCUUGCAUGGUGGAGGG, hsa-miR-2116*: (SEQ ID NO: 268) CCUCCCAUGCCAAGAACUCCC,
hsa-miR-4437: (SEQ ID NO: 269) UGGGCUCAGGGUACAAAGGUU, hsa-miR-4674: (SEQ ID NO: 270) CUGGGCUCGGGACGCGCGGCU, hsa-miR-4725-5p: (SEQ ID NO: 271) AGACCCUGCAGCCUUCCCACC, hsa-miR-4763-5p: (SEQ ID NO: 272) CGCCUGCCCAGCCCUCCUGCU, hsa-miR-5008-3p: (SEQ ID NO: 273) CCUGUGCUCCCAGGGCCUCGC, hsa-miR-5196-3p: (SEQ ID NO: 274) UCAUCCUCGUCUCCCUCCCAG, hsa-miR-5591-3p: (SEQ ID NO: 275) AUACCCAUAGCUUAGCUCCCA, hsa-miR-5591-5p: (SEQ ID NO: 276) UGGGAGCUAAGCUAUGGGUAU, hsa-miR-596: (SEQ ID NO: 277) AAGCCUGCCCGGCUCCUCGGG, hsa-miR-629: (SEQ ID NO: 278) UGGGUUUACGUUGGGAGAACU, hsa-miR-662: (SEQ ID NO: 279) UCCCACGUUGUGGCCCAGCAG, hsa-miR-886-3p: (SEQ ID NO: 280) CGCGGGUGCUUACUGACCCUU, mmu-miR-712: (SEQ ID NO: 281) CUCCUUCACCCGGGCGGUACC, mmu-miR-718: (SEQ ID NO: 282) CUUCCGCCCGGCCGGGUGUCG, hsa-miR-4646-3p: (SEQ ID NO: 283) AUUGUCCCUCUCCCUUCCCAG, hsa-miR-4783-5p: (SEQ ID NO: 284) GGCGCGCCCAGCUCCCGGGCU, hsa-let-7b*: (SEQ ID NO: 285) CUAUACAACCUACUGCCUUCCC, hsa-let-7f-1*: (SEQ ID NO: 286) CUAUACAAUCUAUUGCCUUCCC, hsa-miR-100: (SEQ ID NO: 287) AACCCGUAGAUCCGAACUUGUG, hsa-miR-106b*: (SEQ ID NO: 288) CCGCACUGUGGGUACUUGCUGC, hsa-miR-1180: (SEQ ID NO: 289) UUUCCGGCUCGCGUGGGUGUGU, hsa-miR-125a-3p: (SEQ ID NO: 290) ACAGGUGAGGUUCUUGGGAGCC, hsa-miR-125b-2*: (SEQ ID NO: 291) UCACAAGUCAGGCUCUUGGGAC, hsa-miR-1262: (SEQ ID NO: 292) AUGGGUGAAUUUGUAGAAGGAU, hsa-miR-1263: (SEQ ID NO: 293) AUGGUACCCUGGCAUACUGAGU, hsa-miR-127-5p: (SEQ ID NO: 294) CUGAAGCUCAGAGGGCUCUGAU, hsa-miR-1284: (SEQ ID NO: 295) UCUAUACAGACCCUGGCUUUUC, hsa-miR-1285: (SEQ ID NO: 296) UCUGGGCAACAAAGUGAGACCU, hsa-miR-1293: (SEQ ID NO: 297) UGGGUGGUCUGGAGAUUUGUGC, hsa-miR-1299: (SEQ ID NO: 298) UUCUGGAAUUCUGUGUGAGGGA, hsa-miR-1305: (SEQ ID NO: 299) UUUUCAACUCUAAUGGGAGAGA, hsa-miR-130a: (SEQ ID NO: 300) CAGUGCAAUGUUAAAAGGGCAU, hsa-miR-130b: (SEQ ID NO: 301) CAGUGCAAUGAUGAAAGGGCAU, hsa-miR-135a*: (SEQ ID NO: 302) UAUAGGGAUUGGAGCCGUGGCG, hsa-miR-138-1*: (SEQ ID NO: 303) GCUACUUCACAACACCAGGGCC, hsa-miR-138-2*: (SEQ ID NO: 304) GCUAUUUCACGACACCAGGGUU, hsa-miR-139-3p: (SEQ ID NO: 305) GGAGACGCGGCCCUGUUGGAGU, hsa-miR-140-5p: (SEQ ID NO: 306) CAGUGGUUUUACCCUAUGGUAG, hsa-miR-146a: (SEQ ID NO: 307) UGAGAACUGAAUUCCAUGGGUU, hsa-miR-146b-3p: (SEQ ID NO: 308) UGCCCUGUGGACUCAGUUCUGG, hsa-miR-1471: (SEQ ID NO: 309) GCCCGCGUGUGGAGCCAGGUGU, hsa-miR-183*: (SEQ ID NO: 310) GUGAAUUACCGAAGGGCCAUAA, hsa-miR-184: (SEQ ID NO: 311) UGGACGGAGAACUGAUAAGGGU, hsa-miR-186: (SEQ ID NO: 312) CAAAGAAUUCUCCUUUUGGGCU, hsa-miR-1912: (SEQ ID NO: 313) UACCCAGAGCAUGCAGUGUGAA, hsa-miR-193a-3p: (SEQ ID NO: 314) AACUGGCCUACAAAGUCCCAGU, hsa-miR-196a: (SEQ ID NO: 315) UAGGUAGUUUCAUGUUGUUGGG, hsa-miR-196b: (SEQ ID NO: 316) UAGGUAGUUUCCUGUUGUUGGG, hsa-miR-197: (SEQ ID NO: 317) UUCACCACCUUCUCCACCCAGC, hsa-miR-1977: (SEQ ID NO: 318) GAUUAGGGUGCUUAGCUGUUAA, hsa-miR-1979: (SEQ ID NO: 319) CUCCCACUGCUUCACUUGACUA, hsa-miR-200b*: (SEQ ID NO: 320) CAUCUUACUGGGCAGCAUUGGA, hsa-miR-2000*: (SEQ ID NO: 321) CGUCUUACCCAGCAGUGUUUGG, hsa-miR-204: (SEQ ID NO: 322) UUCCCUUUGUCAUCCUAUGCCU, hsa-miR-20b*: (SEQ ID NO: 323) ACUGUAGUAUGGGCACUUCCAG, hsa-miR-211: (SEQ ID NO: 324) UUCCCUUUGUCAUCCUUCGCCU, hsa-miR-2114: (SEQ ID NO: 325) UAGUCCCUUCCUUGAAGCGGUC, hsa-miR-219-1-3p: (SEQ ID NO: 326) AGAGUUGAGUCUGGACGUCCCG, hsa-miR-220c: (SEQ ID NO: 327) ACACAGGGCUGUUGUGAAGACU, hsa-miR-23b*: (SEQ ID NO: 328) UGGGUUCCUGGCAUGCUGAUUU, hsa-miR-27a*: (SEQ ID NO: 329) AGGGCUUAGCUGCUUGUGAGCA, hsa-miR-299-3p: (SEQ ID NO: 330) UAUGUGGGAUGGUAAACCGCUU, hsa-miR-299-5p: (SEQ ID NO: 331) UGGUUUACCGUCCCACAUACAU,
hsa-miR-300: (SEQ ID NO: 332) UAUACAAGGGCAGACUCUCUCU, hsa-miR-30b*: (SEQ ID NO: 333) CUGGGAGGUGGAUGUUUACUUC, hsa-miR-300-2*: (SEQ ID NO: 334) CUGGGAGAAGGCUGUUUACUCU, hsa-miR-3116: (SEQ ID NO: 335) UGCCUGGAACAUAGUAGGGACU, hsa-miR-3122: (SEQ ID NO: 336) GUUGGGACAAGAGGACGGUCUU, hsa-miR-3124-3p: (SEQ ID NO: 337) ACUUUCCUCACUCCCGUGAAGU, hsa-miR-3126-5p: (SEQ ID NO: 338) UGAGGGACAGAUGCCAGAAGCA, hsa-miR-3133: (SEQ ID NO: 339) UAAAGAACUCUUAAAACCCAAU, hsa-miR-3136-3p: (SEQ ID NO: 340) UGGCCCAACCUAUUCAGUUAGU, hsa-miR-3140-3p: (SEQ ID NO: 341) AGCUUUUGGGAAUUCAGGUAGU, hsa-miR-3156-5p: (SEQ ID NO: 342) AAAGAUCUGGAAGUGGGAGACA, hsa-miR-3157-3p: (SEQ ID NO: 343) CUGCCCUAGUCUAGCUGAAGCU, hsa-miR-3158-3p: (SEQ ID NO: 344) AAGGGCUUCCUCUCUGCAGGAC, hsa-miR-3160-3p: (SEQ ID NO: 345) AGAGCUGAGACUAGAAAGCCCA, hsa-miR-3163: (SEQ ID NO: 346) UAUAAAAUGAGGGCAGUAAGAC, hsa-miR-3164: (SEQ ID NO: 347) UGUGACUUUAAGGGAAAUGGCG, hsa-miR-3173-5p: (SEQ ID NO: 348) UGCCCUGCCUGUUUUCUCCUUU, hsa-miR-3202: (SEQ ID NO: 349) UGGAAGGGAGAAGAGCUUUAAU, hsa-miR-330-5p: (SEQ ID NO: 350) UCUCUGGGCCUGUGUCUUAGGC, hsa-miR-33b*: (SEQ ID NO: 351) CAGUGCCUCGGCAGUGCAGCCC, hsa-miR-345: (SEQ ID NO: 352) GCUGACUCCUAGUCCAGGGCUC, hsa-miR-34a*: (SEQ ID NO: 353) CAAUCAGCAAGUAUACUGCCCU, hsa-miR-3529-5p: (SEQ ID NO: 354) AGGUAGACUGGGAUUUGUUGUU, hsa-miR-3617-5p: (SEQ ID NO: 355) AAAGACAUAGUUGCAAGAUGGG, hsa-miR-3619-3p: (SEQ ID NO: 356) GGGACCAUCCUGCCUGCUGUGG, hsa-miR-3622a-3p: (SEQ ID NO: 357) UCACCUGACCUCCCAUGCCUGU, hsa-miR-3622a-5p: (SEQ ID NO: 358) CAGGCACGGGAGCUCAGGUGAG, hsa-miR-363*: (SEQ ID NO: 359) CGGGUGGAUCACGAUGCAAUUU, hsa-miR-3661: (SEQ ID NO: 360) UGACCUGGGACUCGGACAGCUG, hsa-miR-3667-3p: (SEQ ID NO: 361) ACCUUCCUCUCCAUGGGUCUUU, hsa-miR-3667-5p: (SEQ ID NO: 362) AAAGACCCAUUGAGGAGAAGGU, hsa-miR-3677-3p: (SEQ ID NO: 363) CUCGUGGGCUCUGGCCACGGCC, hsa-miR-3677-5p: (SEQ ID NO: 364) CAGUGGCCAGAGCCCUGCAGUG, hsa-miR-3685: (SEQ ID NO: 365) UUUCCUACCCUACCUGAAGACU, hsa-miR-3689a-3p: (SEQ ID NO: 366) CUGGGAGGUGUGAUAUCGUGGU, hsa-miR-3689a-5p: (SEQ ID NO: 367) UGUGAUAUCAUGGUUCCUGGGA, hsa-miR-3689b-3p: (SEQ ID NO: 368) CUGGGAGGUGUGAUAUUGUGGU, hsa-miR-3689b-5p: (SEQ ID NO: 369) UGUGAUAUCAUGGUUCCUGGGA, hsa-miR-3689c: (SEQ ID NO: 370) CUGGGAGGUGUGAUAUUGUGGU, hsa-miR-3689d: (SEQ ID NO: 371) GGGAGGUGUGAUCUCACACUCG, hsa-miR-3689e: (SEQ ID NO: 372) UGUGAUAUCAUGGUUCCUGGGA, hsa-miR-3689f: (SEQ ID NO: 373) UGUGAUAUCGUGCUUCCUGGGA, hsa-miR-377*: (SEQ ID NO: 374) AGAGGUUGCCCUUGGUGAAUUC, hsa-miR-381: (SEQ ID NO: 375) UAUACAAGGGCAAGCUCUCUGU, hsa-miR-3909: (SEQ ID NO: 376) UGUCCUCUAGGGCCUGCAGUCU, hsa-miR-3913-3p: (SEQ ID NO: 377) AGACAUCAAGAUCAGUCCCAAA, hsa-miR-3913-5p: (SEQ ID NO: 378) UUUGGGACUGAUCUUGAUGUCU, hsa-miR-3923: (SEQ ID NO: 379) AACUAGUAAUGUUGGAUUAGGG, hsa-miR-3934-3p: (SEQ ID NO: 380) UGCUCAGGUUGCACAGCUGGGA, hsa-miR-422a: (SEQ ID NO: 381) ACUGGACUUAGGGUCAGAAGGC, hsa-miR-4298: (SEQ ID NO: 382) CUGGGACAGGAGGAGGAGGCAG, hsa-miR-431*: (SEQ ID NO: 383) CAGGUCGUCUUGCAGGGCUUCU, hsa-miR-433: (SEQ ID NO: 384) AUCAUGAUGGGCUCCUCGGUGU, hsa-miR-4423-5p: (SEQ ID NO: 385) AGUUGCCUUUUUGUUCCCAUGC, hsa-miR-4425: (SEQ ID NO: 386) UGUUGGGAUUCAGCAGGACCAU, hsa-miR-4428: (SEQ ID NO: 387) CAAGGAGACGGGAACAUGGAGC, hsa-miR-4436b-3p: (SEQ ID NO: 388) CAGGGCAGGAAGAAGUGGACAA, hsa-miR-4436b-5p: (SEQ ID NO: 389) GUCCACUUCUGCCUGCCCUGCC, hsa-miR-4467: (SEQ ID NO: 390) UGGCGGCGGUAGUUAUGGGCUU, hsa-miR-4471: (SEQ ID NO: 391) UGGGAACUUAGUAGAGGUUUAA, hsa-miR-4475: (SEQ ID NO: 392) CAAGGGACCAAGCAUUCAUUAU, hsa-miR-4476: (SEQ ID NO: 393) CAGGAAGGAUUUAGGGACAGGC, hsa-miR-448: (SEQ ID NO: 394)
UUGCAUAUGUAGGAUGUCCCAU, hsa-miR-4490: (SEQ ID NO: 395) UCUGGUAAGAGAUUUGGGCAUA, hsa-miR-4496: (SEQ ID NO: 396) GAGGAAACUGAAGCUGAGAGGG, hsa-miR-450b-3p: (SEQ ID NO: 397) UUGGGAUCAUUUUGCAUCCAUA, hsa-miR-4510: (SEQ ID NO: 398) UGAGGGAGUAGGAUGUAUGGUU, hsa-miR-4511: (SEQ ID NO: 399) GAAGAACUGUUGCAUUUGCCCU, hsa-miR-4513: (SEQ ID NO: 400) AGACUGACGGCUGGAGGCCCAU, hsa-miR-4526: (SEQ ID NO: 401) GCUGACAGCAGGGCUGGCCGCU, hsa-miR-4538: (SEQ ID NO: 402) GAGCUUGGAUGAGCUGGGCUGA, hsa-miR-454*: (SEQ ID NO: 403) ACCCUAUCAAUAUUGUCUCUGC, hsa-miR-4632-3p: (SEQ ID NO: 404) UGCCGCCCUCUCGCUGCUCUAG, hsa-miR-4654: (SEQ ID NO: 405) UGUGGGAUCUGGAGGCAUCUGG, hsa-miR-4669: (SEQ ID NO: 406) UGUGUCCGGGAAGUGGAGGAGG, hsa-miR-4681: (SEQ ID NO: 407) AACGGGAAUGCAGGCUGUAUCU, hsa-miR-4690-5p: (SEQ ID NO: 408) GAGCAGGCGAGGCUGGGCUGAA, hsa-miR-4692: (SEQ ID NO: 409) UCAGGCAGUGUGGGUAUCAGAU, hsa-miR-4695-5p: (SEQ ID NO: 410) CAGGAGGCAGUGGGCGAGCAGG, hsa-miR-4717-5p: (SEQ ID NO: 411) UAGGCCACAGCCACCCAUGUGU, hsa-miR-4721: (SEQ ID NO: 412) UGAGGGCUCCAGGUGACGGUGG, hsa-miR-4722-3p: (SEQ ID NO: 413) ACCUGCCAGCACCUCCCUGCAG, hsa-miR-4727-3p: (SEQ ID NO: 414) AUAGUGGGAAGCUGGCAGAUUC, hsa-miR-4729: (SEQ ID NO: 415) UCAUUUAUCUGUUGGGAAGCUA, hsa-miR-4733-3p: (SEQ ID NO: 416) CCACCAGGUCUAGCAUUGGGAU, hsa-miR-4740-5p: (SEQ ID NO: 417) AGGACUGAUCCUCUCGGGCAGG, hsa-miR-4747-5p: (SEQ ID NO: 418) AGGGAAGGAGGCUUGGUCUUAG, hsa-miR-4750-5p: (SEQ ID NO: 419) CUCGGGCGGAGGUGGUUGAGUG, hsa-miR-4755-3p: (SEQ ID NO: 420) AGCCAGGCUCUGAAGGGAAAGU, hsa-miR-4755-5p: (SEQ ID NO: 421) UUUCCCUUCAGAGCCUGGCUUU, hsa-miR-4764-3p: (SEQ ID NO: 422) UUAACUCCUUUCACACCCAUGG, hsa-miR-4768-5p: (SEQ ID NO: 423) AUUCUCUCUGGAUCCCAUGGAU, hsa-miR-4776-5p: (SEQ ID NO: 424) GUGGACCAGGAUGGCAAGGGCU, hsa-miR-4779: (SEQ ID NO: 425) UAGGAGGGAAUAGUAAAAGCAG, hsa-miR-4786-3p: (SEQ ID NO: 426) UGAAGCCAGCUCUGGUCUGGGC, hsa-miR-4788: (SEQ ID NO: 427) UUACGGACCAGCUAAGGGAGGC, hsa-miR-487a: (SEQ ID NO: 428) AAUCAUACAGGGACAUCCAGUU, hsa-miR-487b: (SEQ ID NO: 429) AAUCGUACAGGGUCAUCCACUU, hsa-miR-491-3p: (SEQ ID NO: 430) CUUAUGCAAGAUUCCCUUCUAC, hsa-miR-494: (SEQ ID NO: 431) UGAAACAUACACGGGAAACCUC, hsa-miR-500*: (SEQ ID NO: 432) AUGCACCUGGGCAAGGAUUCUG, hsa-miR-5004-3p: (SEQ ID NO: 433) CUUGGAUUUUCCUGGGCCUCAG, hsa-miR-5004-5p: (SEQ ID NO: 434) UGAGGACAGGGCAAAUUCACGA, hsa-miR-502-3p: (SEQ ID NO: 435) AAUGCACCUGGGCAAGGAUUCA, hsa-miR-504: (SEQ ID NO: 436) AGACCCUGGUCUGCACUCUAUC, hsa-miR-505*: (SEQ ID NO: 437) GGGAGCCAGGAAGUAUUGAUGU, hsa-miR-509-3p: (SEQ ID NO: 438) UGAUUGGUACGUCUGUGGGUAG, hsa-miR-5100: (SEQ ID NO: 439) UUCAGAUCCCAGCGGUGCCUCU, hsa-miR-5193: (SEQ ID NO: 440) UCCUCCUCUACCUCAUCCCAGU, hsa-miR-5583-3p: (SEQ ID NO: 441) GAAUAUGGGUAUAUUAGUUUGG, hsa-miR-5583-5p: (SEQ ID NO: 442) AAACUAAUAUACCCAUAUUCUG, hsa-miR-5585-3p: (SEQ ID NO: 443) CUGAAUAGCUGGGACUACAGGU, hsa-miR-5681a: (SEQ ID NO: 444) AGAAAGGGUGGCAAUACCUCUU, hsa-miR-5681b: (SEQ ID NO: 445) AGGUAUUGCCACCCUUUCUAGU, hsa-miR-5687: (SEQ ID NO: 446) UUAGAACGUUUUAGGGUCAAAU, hsa-miR-5692a: (SEQ ID NO: 447) CAAAUAAUACCACAGUGGGUGU, hsa-miR-5702: (SEQ ID NO: 448) UGAGUCAGCAACAUAUCCCAUG, hsa-miR-5704: (SEQ ID NO: 449) UUAGGCCAUCAUCCCAUUAUGC, hsa-miR-574-3p: (SEQ ID NO: 450) CACGCUCAUGCACACACCCACA, hsa-miR-584: (SEQ ID NO: 451) UUAUGGUUUGCCUGGGACUGAG, hsa-miR-616: (SEQ ID NO: 452) AGUCAUUGGAGGGUUUGAGCAG, hsa-miR-616*: (SEQ ID NO: 453) ACUCAAAACCCUUCAGUGACUU, hsa-miR-617: (SEQ ID NO: 454) AGACUUCCCAUUUGAAGGUGGC, hsa-miR-630: (SEQ ID NO: 455) AGUAUUCUGUACCAGGGAAGGU, hsa-miR-642: (SEQ ID NO: 456) GUCCCUCUCCAAAUGUGUCUUG, hsa-miR-6499-3p:
(SEQ ID NO: 457) AGCAGUGUUUGUUUUGCCCACA, hsa-miR-6499-5p: (SEQ ID NO: 458) UCGGGCGCAAGAGCACUGCAGU, hsa-miR-6501-5p: (SEQ ID NO: 459) AGUUGCCAGGGCUGCCUUUGGU, hsa-miR-6507-3p: (SEQ ID NO: 460) CAAAGUCCUUCCUAUUUUUCCC, hsa-miR-6508-3p: (SEQ ID NO: 461) UGGGCCAUGCAUUUCUAGAACU, hsa-miR-6511a-3p: (SEQ ID NO: 462) CCUCACCAUCCCUUCUGCCUGC, hsa-miR-6512-3p: (SEQ ID NO: 463) UUCCAGCCCUUCUAAUGGUAGG, hsa-miR-654-5p: (SEQ ID NO: 464) UGGUGGGCCGCAGAACAUGUGC, hsa-miR-660: (SEQ ID NO: 465) UACCCAUUGCAUAUCGGAGUUG, hsa-miR-674: (SEQ ID NO: 466) GCACUGAGAUGGGAGUGGUGUA, hsa-miR-7-2*: (SEQ ID NO: 467) CAACAAAUCCCAGUCUACCUAA, hsa-miR-769-5p: (SEQ ID NO: 468) UGAGACCUCUGGGUUCUGAGCU, hsa-miR-885-5p: (SEQ ID NO: 469) UCCAUUACACUACCCUGCCUCU, hsa-miR-888*: (SEQ ID NO: 470) GACUGACACCUCUUUGGGUGAA, hsa-miR-892b: (SEQ ID NO: 471) CACUGGCUCCUUUCUGGGUAGA, hsa-miR-92a: (SEQ ID NO: 472) UAUUGCACUUGUCCCGGCCUGU, hsa-miR-92b: (SEQ ID NO: 473) UAUUGCACUCGUCCCGGCCUCC, hsa-miR-93*: (SEQ ID NO: 474) ACUGCUGAGCUAGCACUUCCCG, hsa-miR-936: (SEQ ID NO: 475) ACAGUAGAGGGAGGAAUCGCAG, hsa-miR-95: (SEQ ID NO: 476) UUCAACGGGUAUUUAUUGAGCA, hsa-miR-99a: (SEQ ID NO: 477) AACCCGUAGAUCCGAUCUUGUG, hsa-miR-99a*: (SEQ ID NO: 478) CAAGCUCGCUUCUAUGGGUCUG, hsa-miR-99b: (SEQ ID NO: 479) CACCCGUAGAACCGACCUUGCG, hsa-miR-99b*: (SEQ ID NO: 480) CAAGCUCGUGUCUGUGGGUCCG, mmu-miR-291a-5p: (SEQ ID NO: 481) CAUCAAAGUGGAGGCCCUCUCU, mmu-miR-291b-5p: (SEQ ID NO: 482) GAUCAAAGUGGAGGCCCUCUCC, mmu-miR-294: (SEQ ID NO: 483) AAAGUGCUUCCCUUUUGUGUGU, mmu-miR-350: (SEQ ID NO: 484) UUCACAAAGCCCAUACACUUUC, mmu-miR-465a-3p: (SEQ ID NO: 485) GAUCAGGGCCUUUCUAAGUAGA, mmu-miR-666-5p: (SEQ ID NO: 486) AGCGGGCACAGCUGUGAGAGCC, mmu-miR-670: (SEQ ID NO: 487) AUCCCUGAGUGUAUGUGGUGAA, mmu-miR-686: (SEQ ID NO: 488) AUUGCUUCCCAGACGGUGAAGA, mmu-miR-695: (SEQ ID NO: 489) AGAUUGGGCAUAGGUGACUGAA, mmu-miR-706: (SEQ ID NO: 490) AGAGAAACCCUGUCUCAAAAAA, mmu-miR-742: (SEQ ID NO: 491) GAAAGCCACCAUGCUGGGUAAA, mmu-miR-761: (SEQ ID NO: 492) GCAGCAGGGUGAAACUGACACA, mmu-miR-763: (SEQ ID NO: 493) CCAGCUGGGAAGAACCAGUGGC, mmu-miR-878-3p: (SEQ ID NO: 494) GCAUGACACCACACUGGGUAGA, mmu-miR-883b-5p: (SEQ ID NO: 495) UACUGAGAAUGGGUAGCAGUCA, rno-miR-349: (SEQ ID NO: 496) CAGCCCUGCUGUCUUAACCUCU, hsa-let-70*: (SEQ ID NO: 497) UAGAGUUACACCCUGGGAGUUA, hsa-miR-1226: (SEQ ID NO: 498) UCACCAGCCCUGUGUUCCCUAG, hsa-miR-125b: (SEQ ID NO: 499) UCCCUGAGACCCUAACUUGUGA, hsa-miR-125b-1*: (SEQ ID NO: 500) ACGGGUUAGGCUCUUGGGAGCU, hsa-miR-1296: (SEQ ID NO: 501) UUAGGGCCCUGGCUCCAUCUCC, hsa-miR-135b*: (SEQ ID NO: 502) AUGUAGGGCUAAAAGCCAUGGG, hsa-miR-150: (SEQ ID NO: 503) UCUCCCAACCCUUGUACCAGUG, hsa-miR-186*: (SEQ ID NO: 504) GCCCAAAGGUGAAUUUUUUGGG, hsa-miR-187*: (SEQ ID NO: 505) GGCUACAACACAGGACCCGGGC, hsa-miR-1915*: (SEQ ID NO: 506) ACCUUGCCUUGCUGCCCGGGCC, hsa-miR-193a-5p: (SEQ ID NO: 507) UGGGUCUUUGCGGGCGAGAUGA, hsa-miR-193b: (SEQ ID NO: 508) AACUGGCCCUCAAAGUCCCGCU, hsa-miR-296-3p: (SEQ ID NO: 509) GAGGGUUGGGUGGAGGCUCUCC, hsa-miR-300-1*: (SEQ ID NO: 510) CUGGGAGAGGGUUGUUUACUCC, hsa-miR-320: (SEQ ID NO: 511) AAAAGCUGGGUUGAGAGGGCGA, hsa-miR-328: (SEQ ID NO: 512) CUGGCCCUCUCUGCCCUUCCGU, hsa-miR-331-5p: (SEQ ID NO: 513) CUAGGUAUGGUCCCAGGGAUCC, hsa-miR-3646: (SEQ ID NO: 514) AAAAUGAAAUGAGCCCAGCCCA, hsa-miR-3938: (SEQ ID NO: 515) AAUUCCCUUGUAGAUAACCCGG, hsa-miR-425*: (SEQ ID NO: 516) AUCGGGAAUGUCGUGUCCGCCC, hsa-miR-4446-3p: (SEQ ID NO: 517) CAGGGCUGGCAGUGACAUGGGU, hsa-miR-4446-5p: (SEQ ID NO: 518) AUUUCCCUGCCAUUCCCUUGGC, hsa-miR-4469: (SEQ ID NO: 519) GCUCCCUCUAGGGUCGCUCGGA,
hsa-miR-4482-5p: (SEQ ID NO: 520) AACCCAGUGGGCUAUGGAAAUG, hsa-miR-4498: (SEQ ID NO: 521) UGGGCUGGCAGGGCAAGUGCUG, hsa-miR-4512: (SEQ ID NO: 522) CAGGGCCUCACUGUAUCGCCCA, hsa-miR-4515: (SEQ ID NO: 523) AGGACUGGACUCCCGGCAGCCC, hsa-miR-4539: (SEQ ID NO: 524) GCUGAACUGGGCUGAGCUGGGC, hsa-miR-4646-5p: (SEQ ID NO: 525) ACUGGGAAGAGGAGCUGAGGGA, hsa-miR-4685-3p: (SEQ ID NO: 526) UCUCCCUUCCUGCCCUGGCUAG, hsa-miR-4713-3p: (SEQ ID NO: 527) UGGGAUCCAGACAGUGGGAGAA, hsa-miR-4713-5p: (SEQ ID NO: 528) UUCUCCCACUACCAGGCUCCCA, hsa-miR-4726-3p: (SEQ ID NO: 529) ACCCAGGUUCCCUCUGGCCGCA, hsa-miR-4733-5p: (SEQ ID NO: 530) AAUCCCAAUGCUAGACCCGGUG, hsa-miR-4734: (SEQ ID NO: 531) GCUGCGGGCUGCGGUCAGGGCG, hsa-miR-4740-3p: (SEQ ID NO: 532) GCCCGAGAGGAUCCGUCCCUGC, hsa-miR-4780: (SEQ ID NO: 533) ACCCUUGAGCCUGAUCCCUAGC, hsa-miR-483-5p: (SEQ ID NO: 534) AAGACGGGAGGAAAGAAGGGAG, hsa-miR-501-3p: (SEQ ID NO: 535) AAUGCACCCGGGCAAGGAUUCU, hsa-miR-501-5p: (SEQ ID NO: 536) AAUCCUUUGUCCCUGGGUGAGA, hsa-miR-5187-5p: (SEQ ID NO: 537) UGGGAUGAGGGAUUGAAGUGGA, hsa-miR-5584-3p: (SEQ ID NO: 538) UAGUUCUUCCCUUUGCCCAAUU, hsa-miR-5584-5p: (SEQ ID NO: 539) CAGGGAAAUGGGAAGAACUAGA, hsa-miR-5685: (SEQ ID NO: 540) ACAGCCCAGCAGUUAUCACGGG, hsa-miR-615-3p: (SEQ ID NO: 541) UCCGAGCCUGGGUCUCCCUCUU, hsa-miR-629*: (SEQ ID NO: 542) GUUCUCCCAACGUAAGCCCAGC, hsa-miR-877*: (SEQ ID NO: 543) UCCUCUUCUCCCUCCUCCCAGG, hsa-miR-887: (SEQ ID NO: 544) GUGAACGGGCGCCAUCCCGAGG, hsa-miR-92b*: (SEQ ID NO: 545) AGGGACGGGACGCGGUGCAGUG, hsa-miR-933: (SEQ ID NO: 546) UGUGCGCAGGGAGACCUCUCCC, hsa-miR-938: (SEQ ID NO: 547) UGCCCUUAAAGGUGAACCCAGU, hsa-miR-1914: (SEQ ID NO: 548) CCCUGUGCCCGGCCCACUUCUG, hsa-miR-3620-3p: (SEQ ID NO: 549) UCACCCUGCAUCCCGCACCCAG, hsa-miR-3940-3p: (SEQ ID NO: 550) CAGCCCGGAUCCCAGCCCACUU, hsa-miR-4687-5p: (SEQ ID NO: 551) CAGCCCUCCUCCCGCACCCAAA, hsa-miR-4747-3p: (SEQ ID NO: 552) AAGGCCCGGGCUUUCCUCCCAG, hsa-miR-874: (SEQ ID NO: 553) CUGCCCUGGCCCGAGGGACCGA, hsa-miR-3620-5p: (SEQ ID NO: 554) GUGGGCUGGGCUGGGCUGGGCC, hsa-miR-103: (SEQ ID NO: 555) AGCAGCAUUGUACAGGGCUAUGA, hsa-miR-107: (SEQ ID NO: 556) AGCAGCAUUGUACAGGGCUAUCA, hsa-miR-10a: (SEQ ID NO: 557) UACCCUGUAGAUCCGAAUUUGUG, hsa-miR-10b: (SEQ ID NO: 558) UACCCUGUAGAACCGAAUUUGUG, hsa-miR-149: (SEQ ID NO: 559) UCUGGCUCCGUGUCUUCACUCCC, hsa-miR-181b: (SEQ ID NO: 560) AACAUUCAUUGCUGUCGGUGGGU, hsa-miR-181d: (SEQ ID NO: 561) AACAUUCAUUGUUGUCGGUGGGU, hsa-miR-18a*: (SEQ ID NO: 562) ACUGCCCUAAGUGCUCCUUCUGG, hsa-miR-191: (SEQ ID NO: 563) CAACGGAAUCCCAAAAGCAGCUG, hsa-miR-1911: (SEQ ID NO: 564) UGAGUACCGCCAUGUCUGUUGGG, hsa-miR-199a-5p: (SEQ ID NO: 565) CCCAGUGUUCAGACUACCUGUUC, hsa-miR-199b-5p: (SEQ ID NO: 566) CCCAGUGUUUAGACUAUCUGUUC, hsa-miR-200c: (SEQ ID NO: 567) UAAUACUGCCGGGUAAUGAUGGA, hsa-miR-221: (SEQ ID NO: 568) AGCUACAUUGUCUGCUGGGUUUC, hsa-miR-3131: (SEQ ID NO: 569) UCGAGGACUGGUGGAAGGGCCUU, hsa-miR-3136-5p: (SEQ ID NO: 570) CUGACUGAAUAGGUAGGGUCAUU, hsa-miR-3161: (SEQ ID NO: 571) CUGAUAAGAACAGAGGCCCAGAU, hsa-miR-3187-5p: (SEQ ID NO: 572) CCUGGGCAGCGUGUGGCUGAAGG, hsa-miR-3192: (SEQ ID NO: 573) UCUGGGAGGUUGUAGCAGUGGAA, hsa-miR-3199: (SEQ ID NO: 574) AGGGACUGCCUUAGGAGAAAGUU, hsa-miR-339-5p: (SEQ ID NO: 575) UCCCUGUCCUCCAGGAGCUCACG, hsa-miR-342-3p: (SEQ ID NO: 576) UCUCACACAGAAAUCGCACCCGU, hsa-miR-346: (SEQ ID NO: 577) UGUCUGCCCGCAUGCCUGCCUCU, hsa-miR-3614-5p: (SEQ ID NO: 578) CCACUUGGAUCUGAAGGCUGCCC, hsa-miR-3616-3p: (SEQ ID NO: 579) CGAGGGCAUUUCAUGAUGCAGGC, hsa-miR-3617-3p: (SEQ ID NO: 580) CAUCAGCACCCUAUGUCCUUUCU, hsa-miR-3663-3p: (SEQ ID NO: 581) UGAGCACCACACAGGCCGGGCGC, hsa-miR-3690: (SEQ ID NO: 582) ACCUGGACCCAGCGUAGACAAAG,
hsa-miR-3922-5p: (SEQ ID NO: 583) UCAAGGCCAGAGGUCCCACAGCA, hsa-miR-3944-3p: (SEQ ID NO: 584) UUCGGGCUGGCCUGCUGCUCCGG, hsa-miR-409-5p: (SEQ ID NO: 585) AGGUUACCCGAGCAACUUUGCAU, hsa-miR-421: (SEQ ID NO: 586) AUCAACAGACAUUAAUUGGGCGC, hsa-miR-425: (SEQ ID NO: 587) AAUGACACGAUCACUCCCGUUGA, hsa-miR-432: (SEQ ID NO: 588) UCUUGGAGUAGGUCAUUGGGUGG, hsa-miR-4461: (SEQ ID NO: 589) GAUUGAGACUAGUAGGGCUAGGC, hsa-miR-454: (SEQ ID NO: 590) UAGUGCAAUAUUGCUUAUAGGGU, hsa-miR-4653-3p: (SEQ ID NO: 591) UGGAGUUAAGGGUUGCUUGGAGA, hsa-miR-4666b: (SEQ ID NO: 592) UUGCAUGUCAGAUUGUAAUUCCC, hsa-miR-4668-5p: (SEQ ID NO: 593) AGGGAAAAAAAAAAGGAUUUGUC, hsa-miR-4683: (SEQ ID NO: 594) UGGAGAUCCAGUGCUCGCCCGAU, hsa-miR-4686: (SEQ ID NO: 595) UAUCUGCUGGGCUUUCUGGUGUU, hsa-miR-4722-5p: (SEQ ID NO: 596) GGCAGGAGGGCUGUGCCAGGUUG, hsa-miR-4726-5p: (SEQ ID NO: 597) AGGGCCAGAGGAGCCUGGAGUGG, hsa-miR-4730: (SEQ ID NO: 598) CUGGCGGAGCCCAUUCCAUGCCA, hsa-miR-4732-5p: (SEQ ID NO: 599) UGUAGAGCAGGGAGCAGGAAGCU, hsa-miR-4742-5p: (SEQ ID NO: 600) UCAGGCAAAGGGAUAUUUACAGA, hsa-miR-4743-5p: (SEQ ID NO: 601) UGGCCGGAUGGGACAGGAGGCAU, hsa-miR-4745-3p: (SEQ ID NO: 602) UGGCCCGGCGACGUCUCACGGUC, hsa-miR-4746-5p: (SEQ ID NO: 603) CCGGUCCCAGGAGAACCUGCAGA, hsa-miR-4754: (SEQ ID NO: 604) AUGCGGACCUGGGUUAGCGGAGU, hsa-miR-4756-5p: (SEQ ID NO: 605) CAGGGAGGCGCUCACUCUCUGCU, hsa-miR-4767: (SEQ ID NO: 606) CGCGGGCGCUCCUGGCCGCCGCC, hsa-miR-492: (SEQ ID NO: 607) AGGACCUGCGGGACAAGAUUCUU, hsa-miR-500: (SEQ ID NO: 608) UAAUCCUUGCUACCUGGGUGAGA, hsa-miR-5003-5p: (SEQ ID NO: 609) UCACAACAACCUUGCAGGGUAGA, hsa-miR-503: (SEQ ID NO: 610) UAGCAGCGGGAACAGUUCUGCAG, hsa-miR-508-5p: (SEQ ID NO: 611) UACUCCAGAGGGCGUCACUCAUG, hsa-miR-5087: (SEQ ID NO: 612) GGGUUUGUAGCUUUGCUGGCAUG, hsa-miR-5089-3p: (SEQ ID NO: 613) AUGCUACUCGGAAAUCCCACUGA, hsa-miR-5188: (SEQ ID NO: 614) AAUCGGACCCAUUUAAACCGGAG, hsa-miR-5589-3p: (SEQ ID NO: 615) UGCACAUGGCAACCUAGCUCCCA, hsa-miR-605: (SEQ ID NO: 616) UAAAUCCCAUGGUGCCUUCUCCU, hsa-miR-635: (SEQ ID NO: 617) ACUUGGGCACUGAAACAAUGUCC, hsa-miR-6506-5p: (SEQ ID NO: 618) ACUGGGAUGUCACUGAAUAUGGU, hsa-miR-6513-5p: (SEQ ID NO: 619) UUUGGGAUUGACGCCACAUGUCU, hsa-miR-657: (SEQ ID NO: 620) GGCAGGUUCUCACCCUCUCUAGG, hsa-miR-668: (SEQ ID NO: 621) UGUCACUCGGCUCGGCCCACUAC, hsa-miR-708: (SEQ ID NO: 622) AAGGAGCUUACAAUCUAGCUGGG, hsa-miR-770-5p: (SEQ ID NO: 623) UCCAGUACCACGUGUCAGGGCCA, hsa-miR-886-5p: (SEQ ID NO: 624) CGGGUCGGAGUUAGCUCAAGCGG, hsa-miR-92a-1*: (SEQ ID NO: 625) AGGUUGGGAUCGGUUGCAAUGCU, hsa-miR-941: (SEQ ID NO: 626) CACCCGGCUGUGUGCACAUGUGC, mmu-miR-207: (SEQ ID NO: 627) GCUUCUCCUGGCUCUCCUCCCUC, hsa-miR-1229: (SEQ ID NO: 628) CUCUCACCACUGCCCUCCCACAG, hsa-miR-1266: (SEQ ID NO: 629) CCUCAGGGCUGUAGAACAGGGCU, hsa-miR-145: (SEQ ID NO: 630) GUCCAGUUUUCCCAGGAAUCCCU, hsa-miR-1538: (SEQ ID NO: 631) CGGCCCGGGCUGCUGCUGUUCCU, hsa-miR-3127-5p: (SEQ ID NO: 632) AUCAGGGCUUGUGGAAUGGGAAG, hsa-miR-3680-3p: (SEQ ID NO: 633) UUUUGCAUGACCCUGGGAGUAGG, hsa-miR-3945: (SEQ ID NO: 634) AGGGCAUAGGAGAGGGUUGAUAU, hsa-miR-4462: (SEQ ID NO: 635) UGACACGGAGGGUGGCUUGGGAA, hsa-miR-4632-5p: (SEQ ID NO: 636) GAGGGCAGCGUGGGUGUGGCGGA, hsa-miR-4656: (SEQ ID NO: 637) UGGGCUGAGGGCAGGAGGCCUGU, hsa-miR-5088: (SEQ ID NO: 638) CAGGGCUCAGGGAUUGGAUGGAG, hsa-miR-602: (SEQ ID NO: 639) GACACGGGCGACAGCUGCGGCCC, hsa-miR-636: (SEQ ID NO: 640) UGUGCUUGCUCGUCCCGCCCGCA, hsa-miR-675: (SEQ ID NO: 641) UGGUGCGGAGAGGGCCCACAGUG, mmu-miR-667: (SEQ ID NO: 642) UGACACCUGCCACCCAGCCCAAG, hsa-miR-1182: (SEQ ID NO: 643) GAGGGUCUUGGGAGGGAUGUGAC, hsa-miR-4640-5p: (SEQ ID NO: 644) UGGGCCAGGGAGCAGCUGGUGGG, hsa-miR-1291: (SEQ ID NO: 645)
UGGCCCUGACUGAAGACCAGCAGU, hsa-miR-1301: (SEQ ID NO: 646) UUGCAGCUGCCUGGGAGUGACUUC, hsa-miR-2277-5p: (SEQ ID NO: 647) AGCGCGGGCUGAGCGCUGCCAGUC, hsa-miR-3132: (SEQ ID NO: 648) UGGGUAGAGAAGGAGCUCAGAGGA, hsa-miR-3138: (SEQ ID NO: 649) UGUGGACAGUGAGGUAGAGGGAGU, hsa-miR-3651: (SEQ ID NO: 650) CAUAGCCCGGUCGCUGGUACAUGA, hsa-miR-3687: (SEQ ID NO: 651) CCCGGACAGGCGUUCGUGCGACGU, hsa-miR-3978: (SEQ ID NO: 652) GUGGAAAGCAUGCAUCCAGGGUGU, hsa-miR-4641: (SEQ ID NO: 653) UGCCCAUGCCAUACUUUUGCCUCA, hsa-miR-4751: (SEQ ID NO: 654) AGAGGACCCGUAGCUGCUAGAAGG, hsa-miR-4769-5p: (SEQ ID NO: 655) GGUGGGAUGGAGAGAAGGUAUGAG, hsa-miR-4793-5p: (SEQ ID NO: 656) ACAUCCUGCUCCACAGGGCAGAGG, hsa-miR-5001-5p: (SEQ ID NO: 657) AGGGCUGGACUCAGCGGCGGAGCU, hsa-miR-5189: (SEQ ID NO: 658) UCUGGGCACAGGCGGAUGGACAGG, hsa-miR-589*: (SEQ ID NO: 659) UCAGAACAAAUGCCGGUUCCCAGA, hsa-miR-619: (SEQ ID NO: 660) GACCUGGACAUGUUUGUGCCCAGU, hsa-miR-661: (SEQ ID NO: 661) UGCCUGGGUCUCUGGCCUGCGCGU, mmu-miR-290-3p: (SEQ ID NO: 662) AAAGUGCCGCCUAGUUUUAAGCCC, hsa-miR-125a-5p: (SEQ ID NO: 663) UCCCUGAGACCCUUUAACCUGUGA, hsa-miR-298: (SEQ ID NO: 664) AGCAGAAGCAGGGAGGUUCUCCCA, hsa-miR-3147: (SEQ ID NO: 665) GGUUGGGCAGUGAGGAGGGUGUGA, hsa-miR-3613-3p: (SEQ ID NO: 666) ACAAAAAAAAAAGCCCAACCCUUC, mmu-miR-351: (SEQ ID NO: 667) UCCCUGAGGAGCCCUUUGAGCCUG, hsa-miR-1273: (SEQ ID NO: 668) GGGCGACAAAGCAAGACUCUUUCUU, hsa-miR-658: (SEQ ID NO: 669) GGCGGAGGGAAGUAGGUCCGUUGGU, hsa-miR-921: (SEQ ID NO: 670) CUAGUGAGGGACAGAACCAGGAUUC, hsa-miR-1292: (SEQ ID NO: 671) UGGGAACGGGUUCCGGCAGACGCUG, hsa-miR-612: (SEQ ID NO: 672) GCUGGGCAGGGCUUCUGAGCUCCUU, hsa-miR-638: (SEQ ID NO: 673) AGGGAUCGCGGGCGGGUGGCGGCCU, hsa-miR-4518: (SEQ ID NO: 674) GCUCAGGGAUGAUAACUGUGCUGAGA, hsa-miR-1183: (SEQ ID NO: 675) CACUGUAGGUGAUGGUGAGAGUGGGCA, hsa-miR-3178: (SEQ ID NO: 676) GGGGCGCGGCCGGAUCG, hsa-miR-4258: (SEQ ID NO: 677) CCCCGCCACCGCCUUGG, hsa-miR-4283: (SEQ ID NO: 678) UGGGGCUCAGCGAGUUU, hsa-miR-4286: (SEQ ID NO: 679) ACCCCACUCCUGGUACC, hsa-miR-4483: (SEQ ID NO: 680) GGGGUGGUCUGUUGUUG, hsa-miR-4534: (SEQ ID NO: 681) GGAUGGAGGAGGGGUCU, hsa-miR-4463: (SEQ ID NO: 682) GAGACUGGGGUGGGGCC, hsa-miR-4492: (SEQ ID NO: 683) GGGGCUGGGCGCGCGCC, hsa-miR-4508: (SEQ ID NO: 684) GCGGGGCUGGGCGCGCG, hsa-miR-4516: (SEQ ID NO: 685) GGGAGAAGGGUCGGGGC, hsa-miR-4532: (SEQ ID NO: 686) CCCCGGGGAGCCCGGCG, hsa-miR-3665: (SEQ ID NO: 687) AGCAGGUGCGGGGCGGCG, hsa-miR-4257: (SEQ ID NO: 688) CCAGAGGUGGGGACUGAG, hsa-miR-4323: (SEQ ID NO: 689) CAGCCCCACAGCCUCAGA, hsa-miR-4514: (SEQ ID NO: 690) ACAGGCAGGAUUGGGGAA, mmu-miR-720: (SEQ ID NO: 691) AUCUCGCUGGGGCCUCCA, hsa-miR-3196: (SEQ ID NO: 692) CGGGGCGGCAGGGGCCUC, hsa-miR-4284: (SEQ ID NO: 693) GGGCUCACAUCACCCCAU, hsa-miR-4292: (SEQ ID NO: 694) CCCCUGGGCCGGCCUUGG, hsa-miR-4466: (SEQ ID NO: 695) GGGUGCGGGCCGGCGGGG, hsa-miR-3180: (SEQ ID NO: 696) UGGGGCGGAGCUUCCGGAG, hsa-miR-4312: (SEQ ID NO: 697) GGCCUUGUUCCUGUCCCCA, hsa-miR-593: (SEQ ID NO: 698) UGUCUCUGCUGGGGUUUCU, hsa-miR-6165: (SEQ ID NO: 699) CAGCAGGAGGUGAGGGGAG, mmu-miR-327: (SEQ ID NO: 700) ACUUGAGGGGCAUGAGGAU, hsa-miR-2861: (SEQ ID NO: 701) GGGGCCUGGCGGUGGGCGG, hsa-miR-4260: (SEQ ID NO: 702) CUUGGGGCAUGGAGUCCCA, hsa-miR-4634: (SEQ ID NO: 703) CGGCGCGACCGGCCCGGGG, hsa-miR-6132: (SEQ ID NO: 704) AGCAGGGCUGGGGAUUGCA, hsa-miR-6090: (SEQ ID NO: 705) GGGGAGCGAGGGGCGGGGC, hsa-miR-1238: (SEQ ID NO: 706) CUUCCUCGUCUGUCUGCCCC, hsa-miR-3187-3p: (SEQ ID NO: 707) UUGGCCAUGGGGCUGCGCGG, hsa-miR-3190-5p:
(SEQ ID NO: 708) UCUGGCCAGCUACGUCCCCA, hsa-miR-324-3p: (SEQ ID NO: 709) ACUGCCCCAGGUGCUGCUGG, hsa-miR-3713: (SEQ ID NO: 710) GGUAUCCGUUUGGGGAUGGU, hsa-miR-4448: (SEQ ID NO: 711) GGCUCCUUGGUCUAGGGGUA, hsa-miR-5739: (SEQ ID NO: 712) GCGGAGAGAGAAUGGGGAGC, hsa-miR-665: (SEQ ID NO: 713) ACCAGGAGGCUGAGGCCCCU, hsa-miR-920: (SEQ ID NO: 714) GGGGAGCUGUGGAAGCAGUA, hsa-miR-1227: (SEQ ID NO: 715) CGUGCCACCCUUUUCCCCAG, hsa-miR-3621: (SEQ ID NO: 716) CGCGGGUCGGGGUCUGCAGG, hsa-miR-4484: (SEQ ID NO: 717) AAAAGGCGGGAGAAGCCCCA, hsa-miR-760: (SEQ ID NO: 718) CGGCUCUGGGUCUGUGGGGA, hsa-miR-1915: (SEQ ID NO: 719) CCCCAGGGCGACGCGGCGGG, hsa-miR-3940-5p: (SEQ ID NO: 720) GUGGGUUGGGGCGGGCUCUG, hsa-miR-4270: (SEQ ID NO: 721) UCAGGGAGUCAGGGGAGGGC, hsa-miR-4651: (SEQ ID NO: 722) CGGGGUGGGUGAGGUCGGGC, hsa-miR-5787: (SEQ ID NO: 723) GGGCUGGGGCGCGGGGAGGU, mmu-miR-705: (SEQ ID NO: 724) GGUGGGAGGUGGGGUGGGCA, hsa-miR-1224-3p: (SEQ ID NO: 725) CCCCACCUCCUCUCUCCUCAG, hsa-miR-1267: (SEQ ID NO: 726) CCUGUUGAAGUGUAAUCCCCA, hsa-miR-1908: (SEQ ID NO: 727) CGGCGGGGACGGCGAUUGGUC, hsa-miR-2355-5p: (SEQ ID NO: 728) AUCCCCAGAUACAAUGGACAA, hsa-miR-3177-3p: (SEQ ID NO: 729) UGCACGGCACUGGGGACACGU, hsa-miR-342-5p: (SEQ ID NO: 730) AGGGGUGCUAUCUGUGAUUGA, hsa-miR-4489: (SEQ ID NO: 731) UGGGGCUAGUGAUGCAGGACG, hsa-miR-4649-3p: (SEQ ID NO: 732) UCUGAGGCCUGCCUCUCCCCA, hsa-miR-4748: (SEQ ID NO: 733) GAGGUUUGGGGAGGAUUUGCU, hsa-miR-4781-5p: (SEQ ID NO: 734) UAGCGGGGAUUCCAAUAUUGG, hsa-miR-486-3p: (SEQ ID NO: 735) CGGGGCAGCUCAGUACAGGAU, hsa-miR-5003-3p: (SEQ ID NO: 736) UACUUUUCUAGGUUGUUGGGG, hsa-miR-3151: (SEQ ID NO: 737) GGUGGGGCAAUGGGAUCAGGU, hsa-miR-331-3p: (SEQ ID NO: 738) GCCCCUGGGCCUAUCCUAGAA, hsa-miR-3648: (SEQ ID NO: 739) AGCCGCGGGGAUCGCCGAGGG, hsa-miR-4322: (SEQ ID NO: 740) CUGUGGGCUCAGCGCGUGGGG, hsa-miR-4667-3p: (SEQ ID NO: 741) UCCCUCCUUCUGUCCCCACAG, hsa-miR-5572: (SEQ ID NO: 742) GUUGGGGUGCAGGGGUCUGCU, hsa-miR-5587-3p: (SEQ ID NO: 743) GCCCCGGGCAGUGUGAUCAUC, mmu-miR-689: (SEQ ID NO: 744) CGUCCCCGCUCGGCGGGGUCC, hsa-miR-1207-5p: (SEQ ID NO: 745) UGGCAGGGAGGCUGGGAGGGG, hsa-miR-1470: (SEQ ID NO: 746) GCCCUCCGCCCGUGCACCCCG, hsa-miR-3162-3p: (SEQ ID NO: 747) UCCCUACCCCUCCACUCCCCA, hsa-miR-3189-3p: (SEQ ID NO: 748) CCCUUGGGUCUGAUGGGGUAG, hsa-miR-4655-3p: (SEQ ID NO: 749) ACCCUCGUCAGGUCCCCGGGG, mmu-miR-702: (SEQ ID NO: 750) UGCCCACCCUUUACCCCGCUC, hsa-miR-10a*: (SEQ ID NO: 751) CAAAUUCGUAUCUAGGGGAAUA, hsa-miR-10b*: (SEQ ID NO: 752) ACAGAUUCGAUUCUAGGGGAAU, hsa-miR-1236: (SEQ ID NO: 753) CCUCUUCCCCUUGUCUCUCCAG, hsa-miR-1303: (SEQ ID NO: 754) UUUAGAGACGGGGUCUUGCUCU, hsa-miR-1323: (SEQ ID NO: 755) UCAAAACUGAGGGGCAUUUUCU, hsa-miR-133a: (SEQ ID NO: 756) UUUGGUCCCCUUCAACCAGCUG, hsa-miR-133b: (SEQ ID NO: 757) UUUGGUCCCCUUCAACCAGCUA, hsa-miR-134: (SEQ ID NO: 758) UGUGACUGGUUGACCAGAGGGG, hsa-miR-185*: (SEQ ID NO: 759) AGGGGCUGGCUUUCCUCUGGUC, hsa-miR-191*: (SEQ ID NO: 760) GCUGCGCUUGGAUUUCGUCCCC, hsa-miR-194*: (SEQ ID NO: 761) CCAGUGGGGCUGCUGUUAUCUG, hsa-miR-198: (SEQ ID NO: 762) GGUCCAGAGGGGAGAUAGGUUC, hsa-miR-2110: (SEQ ID NO: 763) UUGGGGAAACGGCCGCUGAGUG, hsa-miR-223: (SEQ ID NO: 764) UGUCAGUUUGUCAAAUACCCCA, hsa-miR-30d: (SEQ ID NO: 765) UGUAAACAUCCCCGACUGGAAG, hsa-miR-3127-3p: (SEQ ID NO: 766) UCCCCUUCUGCAGGCCUGCUGG, hsa-miR-3144-5p: (SEQ ID NO: 767) AGGGGACCAAAGAGAUAUAUAG, hsa-miR-3150a-3p: (SEQ ID NO: 768) CUGGGGAGAUCCUCGAGGUUGG, hsa-miR-3150b-5p: (SEQ ID NO: 769) CAACCUCGAGGAUCUCCCCAGC, hsa-miR-3152-3p: (SEQ ID NO: 770) UGUGUUAGAAUAGGGGCAAUAA,
hsa-miR-3170: (SEQ ID NO: 771) CUGGGGUUCUGAGACAGACAGU, hsa-miR-3175: (SEQ ID NO: 772) CGGGGAGAGAACGCAGUGACGU, hsa-miR-3179: (SEQ ID NO: 773) AGAAGGGGUGAAAUUUAAACGU, hsa-miR-3180-3p: (SEQ ID NO: 774) UGGGGCGGAGCUUCCGGAGGCC, hsa-miR-3198: (SEQ ID NO: 775) GUGGAGUCCUGGGGAAUGGAGA, hsa-miR-361-5p: (SEQ ID NO: 776) UUAUCAGAAUCUCCAGGGGUAC, hsa-miR-365: (SEQ ID NO: 777) UAAUGCCCCUAAAAAUCCUUAU, hsa-miR-370: (SEQ ID NO: 778) GCCUGCUGGGGUGGAACCUGGU, hsa-miR-3714: (SEQ ID NO: 779) GAAGGCAGCAGUGCUCCCCUGU, hsa-miR-3936: (SEQ ID NO: 780) UAAGGGGUGUAUGGCAGAUGCA, hsa-miR-409-3p: (SEQ ID NO: 781) GAAUGUUGCUCGGUGAACCCCU, hsa-miR-4440: (SEQ ID NO: 782) UGUCGUGGGGCUUGCUGGCUUG, hsa-miR-4450: (SEQ ID NO: 783) UGGGGAUUUGGAGAAGUGGUGA, hsa-miR-4465: (SEQ ID NO: 784) CUCAAGUAGUCUGACCAGGGGA, hsa-miR-4482-3p: (SEQ ID NO: 785) UUUCUAUUUCUCAGUGGGGCUC, hsa-miR-4642: (SEQ ID NO: 786) AUGGCAUCGUCCCCUGGUGGCU, hsa-miR-4652-5p: (SEQ ID NO: 787) AGGGGACUGGUUAAUAGAACUA, hsa-miR-4664-3p: (SEQ ID NO: 788) CUUCCGGUCUGUGAGCCCCGUC, hsa-miR-4667-5p: (SEQ ID NO: 789) ACUGGGGAGCAGAAGGAGAACC, hsa-miR-4675: (SEQ ID NO: 790) GGGGCUGUGAUUGACCAGCAGG, hsa-miR-4700-5p: (SEQ ID NO: 791) UCUGGGGAUGAGGACAGUGUGU, hsa-miR-4701-5p: (SEQ ID NO: 792) UUGGCCACCACACCUACCCCUU, hsa-miR-4714-5p: (SEQ ID NO: 793) AACUCUGACCCCUUAGGUUGAU, hsa-miR-486-5p: (SEQ ID NO: 794) UCCUGUACUGAGCUGCCCCGAG, hsa-miR-5195-5p: (SEQ ID NO: 795) AACCCCUAAGGCAACUGGAUGG, hsa-miR-634: (SEQ ID NO: 796) AACCAGCACCCCAACUUUGGAC, hsa-miR-6505-5p: (SEQ ID NO: 797) UUGGAAUAGGGGAUAUCUCAGC, hsa-miR-6510-5p: (SEQ ID NO: 798) CAGCAGGGGAGAGAGAGGAGUC, hsa-miR-6717-5p: (SEQ ID NO: 799) AGGCGAUGUGGGGAUGUAGAGA, hsa-miR-6723-5p: (SEQ ID NO: 800) AUAGUCCGAGUAACGUCGGGGC, hsa-miR-766: (SEQ ID NO: 801) ACUCCAGCCCCACAGCCUCAGC, hsa-miR-885-3p: (SEQ ID NO: 802) AGGCAGCGGGGUGUAGUGGAUA, mmu-miR-710: (SEQ ID NO: 803) CCAAGUCUUGGGGAGAGUUGAG, rno-miR-664: (SEQ ID NO: 804) UAUUCAUUUACUCCCCAGCCUA, hsa-miR-1234: (SEQ ID NO: 805) UCGGCCUGACCACCCACCCCAC, hsa-miR-129*: (SEQ ID NO: 806) AAGCCCUUACCCCAAAAAGUAU, hsa-miR-129-3p: (SEQ ID NO: 807) AAGCCCUUACCCCAAAAAGCAU, hsa-miR-1469: (SEQ ID NO: 808) CUCGGCGCGGGGCGCGGGCUCC, hsa-miR-18b*: (SEQ ID NO: 809) UGCCCUAAAUGCCCCUUCUGGC, hsa-miR-1909: (SEQ ID NO: 810) CGCAGGGGCCGGGUGCUCACCG, hsa-miR-193b*: (SEQ ID NO: 811) CGGGGUUUUGAGGGCGAGAUGA, hsa-miR-3154: (SEQ ID NO: 812) CAGAAGGGGAGUUGGGAGCAGA, hsa-miR-3972: (SEQ ID NO: 813) CUGCCAGCCCCGUUCCAGGGCA, hsa-miR-4259: (SEQ ID NO: 814) CAGUUGGGUCUAGGGGUCAGGA, hsa-miR-4449: (SEQ ID NO: 815) CGUCCCGGGGCUGCGCGAGGCA, hsa-miR-4652-3p: (SEQ ID NO: 816) GUUCUGUUAACCCAUCCCCUCA, hsa-miR-4655-5p: (SEQ ID NO: 817) CACCGGGGAUGGCAGAGGGUCG, hsa-miR-4664-5p: (SEQ ID NO: 818) UGGGGUGCCCACUCCGCAAGUU, hsa-miR-4688: (SEQ ID NO: 819) UAGGGGCAGCAGAGGACCUGGG, hsa-miR-4707-3p: (SEQ ID NO: 820) AGCCCGCCCCAGCCGAGGUUCU, hsa-miR-4723-3p: (SEQ ID NO: 821) CCCUCUCUGGCUCCUCCCCAAA, hsa-miR-4725-3p: (SEQ ID NO: 822) UGGGGAAGGCGUCAGUGUCGGG, hsa-miR-4749-5p: (SEQ ID NO: 823) UGCGGGGACAGGCCAGGGCAUC, hsa-miR-4769-3p: (SEQ ID NO: 824) UCUGCCAUCCUCCCUCCCCUAC, hsa-miR-484: (SEQ ID NO: 825) UCAGGCUCAGUCCCCUCCCGAU, hsa-miR-491-5p: (SEQ ID NO: 826) AGUGGGGAACCCUUCCAUGAGG, hsa-miR-5008-5p: (SEQ ID NO: 827) UGAGGCCCUUGGGGCACAGUGG, hsa-miR-5010-3p: (SEQ ID NO: 828) UUUUGUGUCUCCCAUUCCCCAG, hsa-miR-5194: (SEQ ID NO: 829) UGAGGGGUUUGGAAUGGGAUGG, hsa-miR-663: (SEQ ID NO: 830) AGGCGGGGCGCCGCGGGACCGC, hsa-miR-744: (SEQ ID NO: 831) UGCGGGGCUAGGGCUAACAGCA, hsa-miR-92a-2*: (SEQ ID NO: 832) GGGUGGGGAUUUGUUGCAUUAC, hsa-miR-1247: (SEQ ID NO: 833) ACCCGUCCCGUUCGUCCCCGGA,
hsa-miR-1914*: (SEQ ID NO: 834) GGAGGGGUCCCGCACUGGGAGG, hsa-miR-23a*: (SEQ ID NO: 835) GGGGUUCCUGGGGAUGGGAUUU, hsa-miR-659: (SEQ ID NO: 836) CUUGGUUCAGGGAGGGUCCCCA, hsa-miR-6722-3p: (SEQ ID NO: 837) UGCAGGGGUCGGGUGGGCCAGG, mmu-miR-711: (SEQ ID NO: 838) GGGACCCGGGGAGAGAUGUAAG, mmu-miR-762: (SEQ ID NO: 839) GGGGCUGGGGCCGGGACAGAGC, hsa-miR-5196-5p: (SEQ ID NO: 840) AGGGAAGGGGACGAGGGUUGGG, hsa-miR-155: (SEQ ID NO: 841) UUAAUGCUAAUCGUGAUAGGGGU, hsa-miR-3184-3p: (SEQ ID NO: 842) AAAGUCUCGCUCUCUGCCCCUCA, hsa-miR-3188: (SEQ ID NO: 843) AGAGGCUUUGUGCGGAUACGGGG, hsa-miR-3191-3p: (SEQ ID NO: 844) UGGGGACGUAGCUGGCCAGACAG, hsa-miR-3675-5p: (SEQ ID NO: 845) UAUGGGGCUUCUGUAGAGAUUUC, hsa-miR-373: (SEQ ID NO: 846) GAAGUGCUUCGAUUUUGGGGUGU, hsa-miR-423-3p: (SEQ ID NO: 847) AGCUCGGUCUGAGGCCCCUCAGU, hsa-miR-423-5p: (SEQ ID NO: 848) UGAGGGGCAGAGAGCGAGACUUU, hsa-miR-4698: (SEQ ID NO: 849) UCAAAAUGUAGAGGAAGACCCCA, hsa-miR-5705: (SEQ ID NO: 850) UGUUUCGGGGCUCAUGGCCUGUG, hsa-miR-6503-5p: (SEQ ID NO: 851) AGGUCUGCAUUCAAAUCCCCAGA, hsa-miR-6511a-5p: (SEQ ID NO: 852) CAGGCAGAAGUGGGGCUGACAGG, hsa-miR-6511b-3p: (SEQ ID NO: 853) CCUCACCACCCCUUCUGCCUGCA, hsa-miR-767-3p: (SEQ ID NO: 854) UCUGCUCAUACCCCAUGGUUUCU, mmu-miR-673-3p: (SEQ ID NO: 855) UCCGGGGCUGAGUUCUGUGCACC, hsa-miR-3153: (SEQ ID NO: 856) GGGGAAAGCGAGUAGGGACAUUU, hsa-miR-324-5p: (SEQ ID NO: 857) CGCAUCCCCUAGGGCAUUGGUGU, hsa-miR-3679-5p: (SEQ ID NO: 858) UGAGGAUAUGGCAGGGAAGGGGA, hsa-miR-4728-5p: (SEQ ID NO: 859) UGGGAGGGGAGAGGCAGCAAGCA, hsa-miR-4741: (SEQ ID NO: 860) CGGGCUGUCCGGAGGGGUCGGCU, hsa-miR-4758-3p: (SEQ ID NO: 861) UGCCCCACCUGCUGACCACCCUC, hsa-miR-4758-5p: (SEQ ID NO: 862) GUGAGUGGGAGCCGGUGGGGCUG, hsa-miR-4783-3p: (SEQ ID NO: 863) CCCCGGUGUUGGGGCGCGUCUGC, hsa-miR-5090: (SEQ ID NO: 864) CCGGGGCAGAUUGGUGUAGGGUG, hsa-miR-611: (SEQ ID NO: 865) GCGAGGACCCCUCGGGGUCUGAC, hsa-miR-671-5p: (SEQ ID NO: 866) AGGAAGCCCUGGAGGGGCUGGAG, hsa-miR-6721-5p: (SEQ ID NO: 867) UGGGCAGGGGCUUAUUGUAGGAG, hsa-miR-769-3p: (SEQ ID NO: 868) CUGGGAUCUCCGGGGUCUUGGUU, hsa-miR-3162-5p: (SEQ ID NO: 869) UUAGGGAGUAGAAGGGUGGGGAG, hsa-miR-4707-5p: (SEQ ID NO: 870) GCCCCGGCGCGGGCGGGUUCUGG, hsa-miR-4745-5p: (SEQ ID NO: 871) UGAGUGGGGCUCCCGGGACGGCG, hsa-miR-623: (SEQ ID NO: 872) AUCCCUUGCAGGGGCUGUUGGGU, hsa-miR-6724-5p: (SEQ ID NO: 873) CUGGGCCCGCGGCGGGCGUGGGG, hsa-miR-3184-5p: (SEQ ID NO: 874) UGAGGGGCCUCAGACCGAGCUUUU, hsa-miR-4697-3p: (SEQ ID NO: 875) UGUCAGUGACUCCUGCCCCUUGGU, hsa-miR-5009-5p: (SEQ ID NO: 876) UUGGACUUUUUCAGAUUUGGGGAU, hsa-miR-6511b-5p: (SEQ ID NO: 877) CUGCAGGCAGAAGUGGGGCUGACA, hsa-miR-3137: (SEQ ID NO: 878) UCUGUAGCCUGGGAGCAAUGGGGU, hsa-miR-4787-3p: (SEQ ID NO: 879) GAUGCGCCGCCCACUGCCCCGCGC, hsa-miR-4649-5p: (SEQ ID NO: 880) UGGGCGAGGGGUGGGCUCUCAGAG, hsa-miR-4763-3p: (SEQ ID NO: 881) AGGCAGGGGCUGGUGCUGGGCGGG, hsa-miR-6089: (SEQ ID NO: 882) GGAGGCCGGGGUGGGGCGGGGCGG, hsa-miR-3180-5p: (SEQ ID NO: 883) CUUCCAGACGCUCCGCCCCACGUCG, hsa-miR-4706: (SEQ ID NO: 884) AGCGGGGAGGAAGUGGGCGCUGCUU, hsa-miR-4728-3p: (SEQ ID NO: 885) CAUGCUGACCUCCCUCCUGCCCCAG, hsa-miR-608: (SEQ ID NO: 886) AGGGGUGGUGUUGGGACAGCUCCGU, hsa-miR-3189-5p: (SEQ ID NO: 887) UGCCCCAUCUGUGCCCUGGGUAGGA, hsa-miR-4739: (SEQ ID NO: 888) AAGGGAGGAGGAGCGGAGGGGCCCU, hsa-miR-4700-3p: (SEQ ID NO: 889) CACAGGACUGACUCCUCACCCCAGUG, hsa-miR-1226*: (SEQ ID NO: 890) GUGAGGGCAUGCAGGCCUGGAUGGGG, hsa-miR-4685-5p: (SEQ ID NO: 891) CCCAGGGCUUGGAGUGGGGCAAGGUU, hsa-miR-1275: (SEQ ID NO: 892) GUGGGGGAGAGGCUGUC, hsa-miR-4447: (SEQ ID NO: 893) GGUGGGGGCUGUUGUUU, hsa-miR-3656: (SEQ ID NO: 894) GGCGGGUGCGGGGGUGG, hsa-miR-1268: (SEQ ID NO: 895) CGGGCGUGGUGGUGGGGG, hsa-miR-4253: (SEQ ID NO: 896)
AGGGCAUGUCCAGGGGGU, hsa-miR-4274: (SEQ ID NO: 897) CAGCAGUCCCUCCCCCUG, hsa-miR-4278: (SEQ ID NO: 898) CUAGGGGGUUUGCCCUUG, hsa-miR-4488: (SEQ ID NO: 899) AGGGGGCGGGCUCCGGCG, hsa-miR-4327: (SEQ ID NO: 900) GGCUUGCAUGGGGGACUGG, hsa-miR-4271: (SEQ ID NO: 901) GGGGGAAGAAAAGGUGGGG, hsa-miR-6085: (SEQ ID NO: 902) AAGGGGCUGGGGGAGCACA, hsa-miR-2392: (SEQ ID NO: 903) UAGGAUGGGGGUGAGAGGUG, hsa-miR-3676-3p: (SEQ ID NO: 904) CCGUGUUUCCCCCACGCUUU, hsa-miR-371-5p: (SEQ ID NO: 905) ACUCAAACUGUGGGGGCACU, hsa-miR-3960: (SEQ ID NO: 906) GGCGGCGGCGGAGGCGGGGG, hsa-miR-4749-3p: (SEQ ID NO: 907) CGCCCCUCCUGCCCCCACAG, hsa-miR-6124: (SEQ ID NO: 908) GGGAAAAGGAAGGGGGAGGA, hsa-miR-4313: (SEQ ID NO: 909) AGCCCCCUGGCCCCAAACCC, hsa-miR-6716-5p: (SEQ ID NO: 910) UGGGAAUGGGGGUAAGGGCC, hsa-miR-1202: (SEQ ID NO: 911) GUGCCAGCUGCAGUGGGGGAG, hsa-miR-1237: (SEQ ID NO: 912) UCCUUCUGCUCCGUCCCCCAG, hsa-miR-4687-3p: (SEQ ID NO: 913) UGGCUGUUGGAGGGGGCAGGC, hsa-miR-5195-3p: (SEQ ID NO: 914) AUCCAGUUCUCUGAGGGGGCU, hsa-miR-625: (SEQ ID NO: 915) AGGGGGAAAGUUCUAUAGUCC, mmu-miR-715: (SEQ ID NO: 916) CUCCGUGCACACCCCCGCGUG, mmu-miR-721: (SEQ ID NO: 917) CAGUGCAAUUAAAAGGGGGAA, hsa-miR-1228*: (SEQ ID NO: 918) GUGGGCGGGGGCAGGUGUGUG, hsa-miR-4433-3p: (SEQ ID NO: 919) ACAGGAGUGGGGGUGGGACAU, mmu-miR-680: (SEQ ID NO: 920) GGGCAUCUGCUGACAUGGGGG, hsa-miR-149*: (SEQ ID NO: 921) AGGGAGGGACGGGGGCUGUGC, hsa-miR-6069: (SEQ ID NO: 922) GGGCUAGGGCCUGCUGCCCCC, hsa-miR-940: (SEQ ID NO: 923) AAGGCAGGGCCCCCGCUCCCC, hsa-miR-150*: (SEQ ID NO: 924) CUGGUACAGGCCUGGGGGACAG, hsa-miR-1913: (SEQ ID NO: 925) UCUGCCCCCUCCGCUGCUGCCA, hsa-miR-3020*: (SEQ ID NO: 926) UUUAACAUGGGGGUACCUGCUG, hsa-miR-3675-3p: (SEQ ID NO: 927) CAUCUCUAAGGAACUCCCCCAA, hsa-miR-373*: (SEQ ID NO: 928) ACUCAAAAUGGGGGCGCUUUCC, hsa-miR-4689: (SEQ ID NO: 929) UUGAGGAGACAUGGUGGGGGCC, hsa-miR-4697-5p: (SEQ ID NO: 930) AGGGGGCGCAGUCACUGACGUG, hsa-miR-4716-3p: (SEQ ID NO: 931) AAGGGGGAAGGAAACAUGGAGA, hsa-miR-4716-5p: (SEQ ID NO: 932) UCCAUGUUUCCUUCCCCCUUCU, hsa-miR-4731-3p: (SEQ ID NO: 933) CACACAAGUGGCCCCCAACACU, hsa-miR-4731-5p: (SEQ ID NO: 934) UGCUGGGGGCCACAUGAGUGUG, hsa-miR-5010-5p: (SEQ ID NO: 935) AGGGGGAUGGCAGAGCAAAAUU, hsa-miR-5698: (SEQ ID NO: 936) UGGGGGAGUGCAGUGAUUGUGG, hsa-miR-625*: (SEQ ID NO: 937) GACUAUAGAACUUUCCCCCUCA, mmu-miR-290-5p: (SEQ ID NO: 938) ACUCAAACUAUGGGGGCACUUU, mmu-miR-292-5p: (SEQ ID NO: 939) ACUCAAACUGGGGGCUCUUUUG, hsa-miR-1225-3p: (SEQ ID NO: 940) UGAGCCCCUGUGCCGCCCCCAG, hsa-miR-4640-3p: (SEQ ID NO: 941) CACCCCCUGUUUCCUGGCCCAC, hsa-miR-4787-5p: (SEQ ID NO: 942) GCGGGGGUGGCGGCGGCAUCCC, hsa-miR-615-5p: (SEQ ID NO: 943) GGGGGUCCCCGGUGCUCGGAUC, hsa-miR-4750-3p: (SEQ ID NO: 944) CCUGACCCACCCCCUCCCGCAG, hsa-miR-361-3p: (SEQ ID NO: 945) UCCCCCAGGUGUGAUUCUGAUUU, hsa-miR-3937: (SEQ ID NO: 946) ACAGGCGGCUGUAGCAAUGGGGG, hsa-miR-3943: (SEQ ID NO: 947) UAGCCCCCAGGCUUCACUUGGCG, hsa-miR-4665-5p: (SEQ ID NO: 948) CUGGGGGACGCGUGAGCGCGAGC, hsa-miR-498: (SEQ ID NO: 949) UUUCAAGCCAGGGGGCGUUUUUC, hsa-miR-4723-5p: (SEQ ID NO: 950) UGGGGGAGCCAUGAGAUAAGAGCA, hsa-miR-637: (SEQ ID NO: 951) ACUGGGGGCUUUCGGGCUCUGCGU, hsa-miR-939: (SEQ ID NO: 952) UGGGGAGCUGAGGCUCUGGGGGUG, hsa-miR-1975: (SEQ ID NO: 953) CCCCCACAACCGCGCUUGACUAGCU, hsa-miR-4665-3p: (SEQ ID NO: 954) CUCGGCCGCGGCGCGUAGCCCCCGCC, hsa-miR-4472: (SEQ ID NO: 955) GGUGGGGGGUGUUGUUUU, hsa-miR-4281: (SEQ ID NO: 956) GGGUCCCGGGGAGGGGGG, hsa-miR-1228: (SEQ ID NO: 957) UCACACCUGCCUCGCCCCCC, hsa-miR-6515-3p: (SEQ ID NO: 958) UCUCUUCAUCUACCCCCCAG, hsa-miR-4525:
(SEQ ID NO: 959) GGGGGGAUGUGCAUGCUGGUU, hsa-miR-4433-5p: (SEQ ID NO: 960) CGUCCCACCCCCCACUCCUGU, hsa-miR-3679-3p: (SEQ ID NO: 961) CUUCCCCCCAGUAAUCUUCAUC, hsa-miR-1225-5p: (SEQ ID NO: 962) GUGGGUACGGCCCAGUGGGGGG, hsa-miR-6087: (SEQ ID NO: 963) UGAGGCGGGGGGGCGAGC, hsa-miR-6088: (SEQ ID NO: 964) AGAGAUGAAGCGGGGGGGCG, hsa-miR-296-5p: (SEQ ID NO: 965) AGGGCCCCCCCUCAAUCCUGU, and hsa-miR-1249: (SEQ ID NO: 966) ACGCCCUUCCCCCCCUUCUUCA (underlines indicate a target GC contiguous sequence).
[0069] The term "target sequence" in the present specification is a sequence contained in a target nucleic acid to which a probe binds, and is a sequence having at least one target GC contiguous sequence. In another expression, the target sequence means a sequence intended to form a double strand with the probe of the present invention, that is, a sequence complementary to a fully complementary probe sequence. The target sequence may be a full length sequence of a target nucleic acid or a partial sequence of a target nucleic acid. For example, the target sequence may have 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 target GC contiguous sequence. In a case where the target sequence has two or more target GC contiguous sequences, these target GC contiguous sequences may be present at a location separated from each other or may be present adjacent to each other as in the example of SEQ ID NO: 873 or SEQ ID NO: 965. A length of the target sequence is 10- to 50-mer. For example, a chain length of the target sequence of the present invention can be 10-mer or more, 11-mer or more, 12-mer or more, 13-mer or more, 14-mer or more, 15-mer or more, 16-mer or more, 17-mer or more, or 18-mer or more. In addition, a chain length of the target sequence of the present invention can be 50-mer or less, 45-mer or less, 40-mer or less, 35-mer or less, 30-mer or less, 29-mer or less, 28-mer or less, 27-mer or less, 26-mer or less, or 25-mer or less. A chain length of the target sequence of the present invention can be 10- to 40-mer, 13- to 30-mer, 15- to 28-mer, or 18- to 25-mer.
[0070] The term "non-target nucleic acid" in the present specification means a nucleic acid of which the presence is not intended to be detected by the probe of the present invention or is intended to be quantitatively determined by the probe of the present invention, and means a nucleic acid having the same GC contiguous sequence as that of a target sequence. The phrase "the same GC contiguous sequence as that of a target sequence" means the same sequence as the GC contiguous sequence that the target sequence has, and means a GC contiguous sequence longer or shorter by one to several bases than the GC contiguous sequence that the target sequence has.
[0071] In addition, the term "non-target sequence" means a sequence that a non-target nucleic acid has, and means a sequence having the same GC contiguous sequence as that of the target sequence.
[0072] In the present specification, the term "specificity" means a proportion of a probe that mistakenly did not bind to a non-target nucleic acid (negative) in a case of binding the probe to a target nucleic acid, and is represented by (the number of non-target nucleic acids that did not bind to probe)/(total number of non-target nucleic acids).
[0073] Furthermore, in the present specification, the term "false positive" means that a probe mistakenly binds to a non-target nucleic acid. In addition, the term "false positive rate" means a rate at which non-target nucleic acids are mistakenly detected as target nucleic acids, and is represented by 1-(specificity), or (the number of non-target nucleic acids to which probe is mistakenly bound)/(total number of non-target nucleic acids). In the present specification, the term "non-specific binding" means that the probe binds to non-target nucleic acids. The term "specific binding" refers to binding of the probe to a target nucleic acid without binding to a non-target nucleic acid. The phrase "the probe does not bind to non-target nucleic acids" is synonymous with "specificity is high" or "high specificity" and "a false positive rate is low". For example, the phrase may mean that a rate of detecting (or quantitatively determining) non-target sequences as a false positive by the probe is low compared to a fully complementary probe, or mean specificity of 0.8, 0.9, 0.95, 0.98, 0.99, or 0.999.
Advantageous Effects of Invention
[0074] The probe of the present invention enables detection or quantitative determination with a low false positive rate in nucleic acid detection, because binding to non-specific sequences occurs less as compared to a probe having a sequence fully complementary to a target sequence. In particular, the probe of the present invention can detect or quantitatively determine short-chain nucleic acids with high specificity by simple double-strand formation without requiring complex processes such as ligation and amplification, because the probe increases a difference in binding power between a target sequence and a non-target sequence by changing binding activity of the probe itself.
BRIEF DESCRIPTION OF THE DRAWINGS
[0075] FIG. 1 shows a diagram in which A of the upper drawing represents a schematic view of a binding aspect with a fully complementary probe sequence (CCC) in a case where a target sequence is GGG, and B of the lower drawing represents a schematic view of a binding aspect with a probe (C*C) of the present invention.
[0076] FIG. 2A is a graph showing results of measuring a Tm value of binding between probe 1 (TCGCCCTCTCAACCCAGCTTTT (SEQ ID NO: 967) -Linker)) and a target/non-target sequence. On the graph, a left vertical axis represents standardized absorbance A (n, T), a right vertical axis represents a first derivative dA (n, T)/dT of the standardized absorbance, and a horizontal axis represents a measurement temperature T [ .degree. C.]. A solid line indicates standardized absorbance A (n, T), and a dotted line indicates a first derivative dA (n, T)/dT of the standardized absorbance.
[0077] FIG. 2B is a graph showing results of measuring a Tm value of binding between probe 2 (TCGCCCTCTCAAC*CAGCTTTT (SEQ ID NO: 968)-Linker) and a target/non-target sequence. A solid line, a dotted line, a left vertical axis, a right vertical axis, and a horizontal axis on the graph are the same as in FIG. 2A.
[0078] FIG. 2C is a graph showing results of measuring a Tm value of binding between probe 3 (TCGC*CTCTCAACCCAGCTTTT (SEQ ID NO: 969)-Linker) and a target/non-target sequence. A solid line, a dotted line, a left vertical axis, a right vertical axis, and a horizontal axis on the graph are the same as in FIG. 2A.
[0079] FIG. 2D is a graph showing results of measuring a Tm value of binding between probe 4 (TCGC*CTCTCAAC*CAGCTTTT (SEQ ID NO: 970)-Linker) and a target/non-target sequence. A solid line, a dotted line, a left vertical axis, a right vertical axis, and a horizontal axis on the graph are the same as in FIG. 2A.
[0080] FIG. 3A is a graph showing results of measuring a Tm value of binding between probe 23-mer and a target/non-target sequence. On the graph, a left vertical axis represents standardized absorbance A (n, T), a right vertical axis represents a first derivative dA (n, T)/dT of the standardized absorbance, and a horizontal axis represents a measurement temperature T [.degree. C]. On the graph, a solid line indicates standardized absorbance A (n, T), and a dotted line indicates a first derivative dA (n, T)/dT of the standardized absorbance.
[0081] FIG. 3B is a graph showing results of measuring a Tm value of binding between probe 18-mer and a target/non-target sequence. A solid line, a dotted line, a left vertical axis, a right vertical axis, and a horizontal axis on the graph are the same as in FIG. 3A.
[0082] FIG. 3C is a graph showing results of measuring a Tm value of binding between probe 17-mer and a target/non-target sequence. A solid line, a dotted line, a left vertical axis, a right vertical axis, and a horizontal axis on the graph are the same as in FIG. 3A.
[0083] FIG. 4 is a view showing a surface of a working electrode in a state of being modified with a probe and HHT.
[0084] FIG. 5 is a view showing the surface of the working electrode in a state of being modified with the probe and HHT, and showing a marker in a state of reaching the surface of the working electrode.
[0085] FIG. 6 is a graph showing a CV waveform when the surface of the working electrode is modified with the probe and HHT. On the graph, a vertical axis indicates a current, and a horizontal axis indicates a voltage.
[0086] FIG. 7 shows results of adding only non-target sequences as a sample to the state of FIG. 6. It is a graph showing the surface of the working electrode in a state of being modified with the probe and HHT, and showing a CV waveform at the time of a marker in a state of reaching the surface of the working electrode, because no nucleic acid that hybridizes with the probe is present. On the graph, a vertical axis indicates a current, and a horizontal axis indicates a voltage.
[0087] FIG. 8 is a view showing a state in which the surface of the working electrode is modified with the probe and HHT, the probe and a nucleic acid are hybridized, and a marker is unlikely to reach the surface of the working electrode.
[0088] FIG. 9 is a graph showing a CV waveform at the time of a state in which the surface of the working electrode is modified with the probe and HHT, the probe and a nucleic acid are hybridized, and a marker is unlikely to reach the surface of the working electrode. On the graph, a vertical axis indicates a current, and a horizontal axis indicates a voltage.
[0089] FIG. 10A is a graph showing a CV waveform when each of a target sequence and a non-target sequence is modified with respect to probe 1. On the graph, a vertical axis indicates a current, and a horizontal axis indicates a voltage.
[0090] FIG. 10B is a graph showing a CV waveform when each of a target sequence and a non-target sequence is modified with respect to probe 2. On the graph, a vertical axis indicates a current, and a horizontal axis indicates a voltage.
[0091] FIG. 10C is a graph showing a CV waveform when each of a target sequence and a non-target sequence is modified with respect to probe 3. On the graph, a vertical axis indicates a current, and a horizontal axis indicates a voltage.
[0092] FIG. 10D is a graph showing a CV waveform when each of a target sequence and a non-target sequence is modified with respect to probe 4. On the graph, a vertical axis indicates a current, and a horizontal axis indicates a voltage.
[0093] FIG. 11A is a graph showing a CV waveform when each of a target sequence and a non-target sequence is modified with respect to probe 23-mer. On the graph, a vertical axis indicates a current, and a horizontal axis indicates a voltage.
[0094] FIG. 11B is a graph showing a CV waveform when each of a target sequence and a non-target sequence is modified with respect to probe 18-mer. On the graph, a vertical axis indicates a current, and a horizontal axis indicates a voltage.
[0095] FIG. 11C is a graph showing a CV waveform when each of a target sequence and a non-target sequence is modified with respect to probe 17-mer. On the graph, a vertical axis indicates a current, and a horizontal axis indicates a voltage.
DESCRIPTION OF EMBODIMENTS
[0096] 1. Method for Designing Polynucleobase Probe
[0097] In one embodiment, the present invention relates to a method for designing a polynucleobase probe sequence that is capable of binding, with high specificity, to a target nucleic acid having a target sequence having at least one sequence of SEQ ID NOs: 1 to 10 (a GC contiguous sequence), the method including:
[0098] A) selecting a 10- to 50-mer sequence fully complementary to the target sequence as a fully complementary probe sequence; and
[0099] B) (i) in the fully complementary probe sequence, designing the polynucleobase probe by substituting or making at least one of bases abasic in a portion complementary to the GC contiguous sequence in the target sequence, and/or
[0100] B) (ii) in the fully complementary probe sequence, designing the polynucleobase probe sequence by cleaving the fully complementary probe sequence such that a portion complementary to the GC contiguous sequence in the target sequence becomes 2 bases or less.
[0101] Preferably, the polynucleobase probe sequence of the present invention is designed by creating an abasic site, substituting, or cleaving such that the number of bases in which any one of guanine or cytosine is contiguous becomes two bases or less, in the polynucleobase sequence (a probe GC contiguous sequence) complementary to a target GC contiguous sequence in the probe sequence.
[0102] In the method of the present invention, a target sequence is contained in a target nucleic acid, and any sequence containing at least one GC contiguous sequence can be selected. A length of the target sequence is not particularly limited as long as specific detection of a target nucleic acid is possible, and can be a length of the target sequence described above. The fully complementary probe sequence can be obtained as a polynucleobase sequence that is fully complementary to the target sequence.
[0103] As a position and the number of bases to become abasic or be substituted, it is possible to adopt any of substitution/abasic site in the above-mentioned probe GC contiguous sequence of the present invention. "Abasic site creation" can be carried out by substituting a base site with a hydrogen atom, a hydroxyl group, a lower alkyl group, a lower acyl group or the like. In a case of PNA, creating an abasic site may be carried out by substituting a nitrogen atom of a glycine skeleton with a carbon atom (which may have a lower acyl group (such as an acetyl group) or a lower alkyl group (such as a methyl group) as a substituent). In addition, "substitution" can be carried out by substituting a base site with a non-complementary base (such as a natural base or an artificial base), or may be carried out by substituting a base site with a group such as a phenyl group and an anthraquinone group, which does not inhibit the formation of a double helix structure with another base. A substituted/abasic probe sequence is preferably designed to not to have a probe GC contiguous sequence.
[0104] Cleavage of a fully complementary probe sequence is carried out by cleaving the fully complementary probe sequence within a probe GC contiguous sequence. Cleavage is performed at a position at which a fragment intended to be utilized as a polynucleobase probe has, at the end thereof, two or less bases of guanine or cytosine derived from a probe GC contiguous sequence, among fragments obtained by cleavage. Accordingly, a polynucleobase probe obtained by cleavage has one or two bases of guanine or one or two bases of cytosine at one or both ends.
[0105] In a case where the fully complementary probe sequence has two or more probe GC contiguous sequences, a polynucleobase probe sequence may be designed by performing the substitution, creating an abasic site, and cleavage described above alone or in combination at the two or more GC contiguous sequences. The substitution, creating an abasic site, and cleavage are preferably performed in all probe GC contiguous sequences in the probe in the design of the present invention. Accordingly, the polynucleobase probe sequence is preferably designed to not to have a probe GC contiguous sequence.
[0106] In the present specification, "binding, detecting, or quantitatively determining with high specificity" or "specifically detecting/binding" a target sequence having at least one GC contiguous sequence means detection (or quantitative determination) of a non-target sequence as a false positive at a low rate, compared to a probe (in which substituting or creating an abasic site has not been performed) complementary to a target sequence (a probe having a fully complementary probe sequence, hereinafter referred to as a "fully complementary probe"). Regarding whether or not a rate at which a test probe detects (or quantitatively determines) non-target sequences as false positives is low compared to a fully complementary probe, for example, in a case where a Tm value of the test probe is lower than a Tm value of the fully complementary probe by measuring a temperature at which 50% of double strands dissociate into single strands (melting temperature: Tm value) when binding of both probes to non-target sequences; or in a case where a Tm value of the test probe cannot be measured (no formation of a double strand), it can be determined that a rate at which the test probe detects (or quantitatively determines) non-target sequences as false positives is low compared to the fully complementary probe. Alternatively, this may mean binding, detecting, or quantitatively determining with a specificity of 0.8, 0.9, 0.95, 0.98, 0.99, 0.999, or the like.
[0107] 2. Production of Polynucleobase Probe
[0108] As the polynucleobase probe according to the present invention, a probe designed by the above-described design method can be produced by utilizing methods known in the technical field. In particular, methods of chemical synthesis in which polynucleobases such as DNA/RNA, PNA, and LNA are bound one by one are well known, and such methods can be adopted. For example, in a case of PNA, using an Fmoc solid phase synthesis method, a base can be substituted with a carbon skeleton by elongating with 5-[(9-Fluorenylmethoxycarbonyl)amino] pentanoic acid, instead of elongating a site to become abasic with a base. In addition, if necessary, a synthesized polynucleobase probe can be bound to a modifier such as a solid phase or a label.
[0109] 3. Method for Detecting or Quantitatively Determining Target Nucleic Acid having GC Contiguous Sequence using Polynucleobase Probe According to the Present Invention
[0110] In another aspect, the present invention relates to a method for detecting a target nucleic acid having at least one sequence of any one of SEQ ID NOs: 1 to 10 in a test sample with high specificity, the method including:
[0111] preparing the test sample to detect the target nucleic acid;
[0112] contacting at least one kind of the polynucleobase probes according to the present invention with the test sample; and
[0113] detecting the target nucleic acid bound to the polynucleobase probe.
[0114] In another aspect, the present invention relates to a method for quantitatively determining a target nucleic acid having at least one sequence of any one of SEQ ID NOs: 1 to 10 in a test sample with high specificity, the method including:
[0115] preparing the test sample to quantitatively determine the target nucleic acid;
[0116] contacting at least one kind of the polynucleobase probes according to the present invention with the test sample; and
[0117] quantitatively determining the target nucleic acid bound to the polynucleobase probe.
[0118] In the detection method and quantitative determination method of the present invention, a test sample can be prepared by using a target sample from which the presence or an amount of a target nucleic acid that is to be detected or quantitatively determined is examined. For example, for diagnostic purposes, the target sample is not particularly limited as long as it is a sample from which DNA or RNA can be detected, and it is possible to use body fluids or tissues such as lymph fluid, blood (serum, plasma), urine, feces, saliva, spinal fluid, tears, biopsy, hair, skin, nails, leachates, and cells (such as circulating tumor cells in blood (CTC)); exosomes; or cell-free DNA. These samples are appropriately prepared as samples suitable for detection of DNA or RNA.
[0119] Contact between at least one type of the polynucleobase probes according to the present invention and the test sample can be performed by, for example, mixing the polynucleobase probe according to the present invention and the test sample in a buffer. In particular, in a case where the polynucleobase probe according to the present invention is bound to a solid phase, the polynucleobase probe can be brought into contact in a static state, or can be dynamically brought into contact by a microfluidic device or the like.
[0120] For detection or quantitative determination of a target nucleic acid bound to a polynucleobase probe, methods widely known in the field of nucleic acid detection can be adopted. In a case where a label is bound to the probe, a detection method and a quantitative determination method can be adopted according to the type of the label. In addition, in a case where the label is not bound to the probe, it is possible to perform electrical detection or quantitative determination by using an intercalating agent inserted into a double strand (refer to, for example, Japanese Unexamined Patent Publication No. 2006-061061).
[0121] 4. Another Method for Utilizing Polynucleobase Probe According to the Present Invention
[0122] In addition to the detection and quantitative determination methods in which direct measurement is performed after hybridization as described above, the probe of the present invention can also be used in detection and quantitative determination methods by utilizing amplification and ligation after utilizing hybridization. In particular, in a case of utilizing amplification, the probe can be used as a primer. In addition, the probe of the present invention can be used as an antisense DNA. Such an antisense DNA can be used for knockout/knockdown of gene expression. Furthermore, such an antisense DNA can be used for therapeutic purposes, for example, for gene therapy.
[0123] For example, the probe according to the present invention can be used in the following method:
[0124] A method for detecting or quantitatively determining a target nucleic acid in a test sample with high specificity, compared to detection and quantitative determination which use a probe (primer) complementary to a target sequence having at least one sequence of any one of SEQ ID NOs: 1 to 10, the method including:
[0125] preparing the test sample to quantitatively determine the target nucleic acid;
[0126] contacting at least one kind of the polynucleobase probes (primers) according to the present invention with the test sample;
[0127] amplifying a nucleic acid complementary to the target nucleic acid; and
[0128] detecting or quantitatively determining the amplified target nucleic acid.
[0129] Alternatively, the probe according to the present invention can be used in the following method:
[0130] A method for detecting or quantitatively determining a target nucleic acid in a test sample with high specificity, compared to detection and quantitative determination which use a probe complementary to a target sequence having at least one sequence of any one of SEQ ID NOs: 1 to 10, the method including:
[0131] preparing the test sample to quantitatively determine the target nucleic acid;
[0132] contacting, with the test sample, (i) at least one type of the polynucleobase probes according to the present invention, and (ii) a complementary probe that does not have a target sequence overlapping with the polynucleobase probe according to the present invention, in which bases separated by one to several bases from the target sequence of the polynucleobase probe according to the present invention are at the end of the target sequence;
[0133] binding by ligation of two types of probes forming a complementary strand with the target nucleic acid; and
[0134] detecting or quantitatively determining a bound substance of the two types of probes.
EXAMPLES
[0135] Hereinafter, the present invention will be specifically explained based on examples, but the present invention is not limited thereto. The present application claims priority right based on Japanese Patent Application No. 2017-030553 filed Feb. 22, 2017, and the contents described in the application are incorporated in the present specification by reference in their entirety. In addition, the contents described in all of the patents, patent applications, and documents cited in the present application are incorporated in the present specification by reference in their entirety.
Example 1
Tm Value Determination Method
[0136] Absorbance at 260 nm and 320 nm of each cell was measured while changing a temperature, and a Tm value of a double strand formed by a probe and a target was determined from the obtained data of absorbance with respect to a temperature. A measuring device of an amount of change in absorbance, and conditions were as follows. Absorbance measurements were performed during annealing and Tm value measurements according to measurement software settings.
[0137] Measuring Device
[0138] Spectrophotometer UV-2600 (manufactured by Shimadzu Corporation)
[0139] Temperature controller TMSPC-8 (manufactured by Shimadzu Corporation)
[0140] 8 Multicell 208-92097-11 (manufactured by Shimadzu Corporation) Measurement software UVProbe ver. 2.52 (manufactured by Shimadzu Corporation)
[0141] Constant Temperature Bath CCA-1111 (manufactured by EYERA)
[0142] Measurement software setting
[0143] Standby time before absorbance measurement: 4 minutes
[0144] Absorbance measurement interval: 1.degree. C.
[0145] Slit width: 1.0 nm
[0146] Cumulative time: 3
[0147] Temperature blank
[0148] SSC (1.times.)
[0149] 20% DMSO aqueous solution
[0150] Measurement sample
[0151] SSC (1.times.)
[0152] 20% DMSO aqueous solution
[0153] Probe 2 .mu.M
[0154] Target 2 .mu.M
[0155] SSC: Saline Sodium Citrate Buffer
[0156] Specifically, cells to which a nucleic acid sample in which each of probes/targets to be measured are combined, or a temperature blank is added were allowed to stand by before annealing at 95.degree. C. for 10 minutes, and then cooled from 95.degree. C. to 20.degree. C. at 0.5.degree. C./min to be annealed. Thereafter, after standing by before Tm value measurement at 20.degree. C. for 60 minutes, the temperature was raised from 20.degree. C. to 95.degree. C. at 0.5.degree. C./min to measure the Tm value. A baseline was measured using a temperature blank. Using the data of the temperature blank cell, baseline correction was performed on a wavelength range of 330 nm to 250 nm.
[0157] Based on the obtained absorbance at two wavelengths (260 nm and 320 nm), two-wavelength correction was performed by subtracting environment-dependent absorbance variation A320 (n, T) from absorbance A260 (n, T) of the nucleic acid in the sample, and temperature-corrected absorbance Aw was calculated.
Aw (n, T)=A260(n, T)-A320(n, T)
[0158] n: Cell number (n=1, 2, . . . , 8)
[0159] T: Temperature at measurement (T =20, 21, . . . , 95)
[0160] Aw (n, T): Temperature-corrected absorbance at temperature T of cell number n
[0161] A260 (n, T): Absorbance at a wavelength of 260 nm at temperature T of cell number n
[0162] A320 (n, T): Absorbance at a wavelength of 320 nm at temperature T of cell number n
[0163] Furthermore, in order to remove the absorbance variation due to the temperature change of the solvent, temperature correction was performed by subtracting Aw (1, T) of the temperature blank cell from Aw (n, T) of the nucleic acid sample, and temperature-blank-corrected absorbance At was calculated.
At (n, T)=Aw (n, T)-Aw (1, T)
[0164] At (n, T): Temperature-blank-corrected absorbance of cell number n
[0165] Standardized absorbance A was calculated by standardizing the obtained At (n, T) such that a maximum value thereof became 1. Accordingly, Max (A (n, T))=1.
A (n, T)=At (n, T)/Max (At (n, T))
[0166] A (n, T): Standardized absorbance
[0167] Max (At (n, T)): Maximum value of cell number n at At (n, T)
[0168] Based on A (n, T) obtained by the above calculation, an amount of change in absorbance [%] .DELTA. A abs (n) of cell number n showing an amount of base pairs formed, and a maximum value Tm (n) of a first derivative due to a temperature of cell number n which shows a Tm value [.degree. C.] were obtained according to the following equation. In the following equation, Min (At (n, T)) represents a minimum value at At (n, T) of cell number n.
.DELTA.abs (n)=(Max(A(n, T))-Min (A(n, T)))*100
[0169] Tm (n)=Max (dA (n, T)/dT)
Example 2
Abasic Probe
[0170] Abasic site creation was performed by substituting a part of the probe using PNA which is one embodiment of the present invention with 5-aminopentanoic acid (hereinafter Ape). Hereinafter, the term "Linker" represents a structure including a thiol group for binding a probe to a gold electrode. A target GC contiguous sequence in the present example was GGG, and the probe GC contiguous sequence was CCC. A substitution site with Ape is indicated by "*".
[0171] FIG. 1A shows a state in which no abasic site is contained, and in which CCC of a PNA probe (a lower part in the drawing) and GGG of a target RNA (an upper part in the drawing) form a base pair. FIG. 1B shows a state in which an abasic site by substitution of cytosine with Ape is applied, and in which C*C of a probe (a lower part in the drawing) and GGG of an RNA in the sample (an upper part in the drawing) do not form a base pair partially.
[0172] In order to confirm effects of abasic sites, using four types of probes 1 to 4 which have the following sequences, Tm values with respect to base pair formation by a target sequence (a sequence complementary to a probe) and a non-target sequence (a sequence not complementary to a probe) were measured by the method described above. Non-target sequences have sequences that are not complementary to the probe, but contain the same GC contiguous sequence (GGG) as the target sequence. For this reason, non-target sequences are likely to form base pairs with the probes, and base pair formation by non-target sequences and the probes means a false positive.
[0173] (Target Sequence and Non-Target Sequence)
TABLE-US-00002 (SEQ ID NO: 971) Target sequence: AAAAGCUGGGUUGAGAGGGCGA (SEQ ID NO: 972) Non-target sequence: UGGCAGGGAGGCUGGGAGGGG (Probe) (SEQ ID NO: 967) Probe 1: TCGCCCTCTCAACCCAGCTTTT-Linker (SEQ ID NO: 968) Probe 2: TCGOCCTCTCAAC*CAGCTTTT-Linker (SEQ ID NO: 969) Probe 3: TCGC*CTCTCAACCCAGCTTTT-Linker (SEQ ID NO: 970) Probe 4: TCGC*CTCTCAAC*CAGCTTTT-Linker
[0174] The results of measuring Tm values of eight combinations of the probe and the target/non-target sequences by the method shown in Example 1 are shown in FIGS. 2A to 2D. A Tm value for binding of probe 1 to a non-target sequence is 58.degree. C. Aabs was as high as 10% which indicates that probe 1 formed a base pair with a non-target sequence which is originally a non-complementary strand. On the other hand, in the case of abasic probes 2, 3 and 4, a difference appeared in Aabs with respect to a non-target sequence, and a decreasing tendency was further observed in the probe 4 including two abasic sites which is compared with the probes 2 and 3 including one abasic site. It is shown that non-specific base pair formation (a false positive) by non-target sequences with target sequences having two or more GC contiguous sequences can be effectively reduced by using a probe (a site-2-substituted probe) in which a portion complementary to both GC contiguous sequences in the complementary probe is substituted with Ape. In probe 4, the variation of dA (n, T)/dT in base pair formation with a non-target sequence is a noise level, and a Tm value could not be obtained. Accordingly, probe 4 is perceived not to bind to a non-target sequence at any temperature. On the other hand, a Tm value for a target sequence tended to decrease in accordance with an increase of the abasic site, but in the two-sites-substituted probe, a Tm value was 58.degree. C., and Aabs was also high. Based on the above description, it was confirmed that the double strand was formed with the target without problems. Therefore, it was shown that detection of a target sequence with a low false positive rate is possible by appropriately controlling a temperature using an abasic probe.
Example 3
Probes with Different Chain Lengths
[0175] As described in Example 2 above, it was shown that an abasic site of a GC contiguous sequence effectively enables detection with low false positive rate by an experiment using an abasic probe in which bases in the sequence are deleted. Based on the above description, it was examined whether or not detection with low false positive rate is possible with a probe in which a sequence length was shortened by cleaving in the middle of the GC contiguous sequence, in the sequence in which the GC contiguous sequence is present near the end.
[0176] Specifically, the GC contiguous sequence in the probe using PNA, which is one embodiment of the present invention, was cleaved, and three types of probes which have different chain lengths and have the following sequences were prepared. Tm values were measured by the method described above with respect to base pair formation by target sequences (sequences complementary to probes) and non-target sequences (sequences not complementary to probes). Non-target sequences have sequences that are not complementary to the probe, but contain the same GC contiguous sequence (GGG) as the target sequence. For this reason, non-target sequences are likely to form base pairs with the probes, and base pair formation with the probes means a false positive. A target GC contiguous sequence in the present example was GGG, and the complementary probe GC contiguous sequence was CCC.
[0177] (Target Sequence and Non-Target Sequence)
TABLE-US-00003 (SEQ ID NO: 973) Target sequence: AGCUACAUUGUCUGCUGGGUUUC (SEQ ID NO: 974) Non-target sequence: UGGCAGGGAGGCUGGGAGGGG (Probe) (SEQ ID NO: 975) Probe 23-mer: GAAACCCAGCAGACAATGTAGCT-Linker (SEQ ID NO: 976) Probe 18-mer: CCAGCAGACAATGTAGCT-Linker (SEQ ID NO: 977) Probe 17-mer: CAGCAGACAATGTAGCT-Linker
[0178] The results of measuring Tm values of six combinations of the probe and the target/non-target sequences by the method shown in Example 1 are shown in FIGS. 3A to 3C.
[0179] A large difference is shown in Aabs with respect to non-target sequences between probe 23-mer and probe 18-mer or probe 17-mer. However, no difference is shown between the probe 18-mer and the probe 17-mer, and it was shown that a base pair with a non-target sequence is hardly formed merely by making one base short from three consecutive cytosines. On the other hand, a Tm value for the target sequence tended to decrease as a chain length was shortened, but in the 17-mer probe, the Tm value is 70.degree. C., and Aabs is also high. Accordingly, it was confirmed that a double strand was formed with the target. Therefore, it is shown that, in a case where GC contiguous sequences are present near the end of the probe or target sequence, an effect of reducing non-specific base pair formation (a false positive) with non-target sequences is exhibited by shortening of a probe chain length. In probe 18-mer and probe 17-mer, the variation of dA (n, T)/dT in base pair formation with a non-target sequence is a noise level, and a Tm value could not be obtained. Accordingly, probe 18-mer and probe 17-mer are perceived not to bind to a non-target sequence at any temperature. Therefore, it was shown that detection of a target sequence with a low false positive rate is possible by appropriately controlling a temperature using a short chain probe.
Example 4
Establishment of Method for Detecting Nucleic Acid by Electrochemical Measurement
[0180] In the present example, the term "modification" refers to a process of dropwise adding of a corresponding solution on a working electrode by a pipette and then allowing it to stand at a designated temperature for a designated time. In addition, in the present example, the term "washing" refers to a process of washing a surface of a gold electrode with a designated washing solution at a designated temperature.
[0181] (1) Adjustment of Measurement Solution
[0182] A pH of a sodium dihydrogen phosphate aqueous solution was adjusted to become 7.0 with sodium hydroxide, and then sodium perchlorate and potassium hexacyanoferrate (II) were added thereto. A final concentration of the measurement solution was 2.5 mM of sodium dihydrogen phosphate, 5 mM of sodium perchlorate, and 1 mM of potassium hexacyanoferrate (II).
[0183] (2) Measurement Method
[0184] The electrochemical measurement in the present example was performed by the following steps. In the following table, RT represents room temperature (about 25.degree. C.), TFA represents trifluoroacetic acid, DMSO represents dimethyl sulfoxide, and Milli-Q represents ultra pure water.
TABLE-US-00004 TABLE 1 Concen- Temper- Amount of tration of Process Time ature Solvent solution solute 1. Probe 30 min. 25.degree. C. 0.05% 10 ul 10 uM modification TFA aq 2. Washing 80.degree. C. 20% 100 ml DMSO aq 3. HHT 30 min. 25.degree. C. Milli-Q 25 ul 1 mM modification 4. Washing RT Milli-Q 50 ml 5. Measure- RT Measure- 1 ml ment 1 ment solution 6. Sample 40 min. 40.degree. C. 1*SSC, 250 ul 25 nM modification 20% DMSO aq 7. Washing RT Milli-Q 50 ml 8. Washing 50.degree. C. Milli-Q 100 ml 9. Measure- RT Measure- 1 ml ment 1 ment (*1)
[0185] As a sample, a solution containing any one of a target nucleic acid or a non-target nucleic acid which has a specified concentration was used. The measurement was carried out by cyclic voltammetry (hereinafter, CV) by using working electrode: gold electrode with a diameter of 300 .mu.m, counter electrode: Pt counter electrode of 5 cm manufactured by BAS, reference electrode: RE-1B aqueous reference electrode (Ag/AgCl) manufactured by BAS, Potentiostat (miniSTAT 100 manufactured by BioDevice Technology). The measurement conditions (miniStat 100 setting contents) were as follows.
TABLE-US-00005 TABLE 2 Control software parameter name Setting value Commentary Begin potential -150 mV Initial voltage First vertex potential 500 mV Firstly reached voltage Second vertex potential -150 mV Secondly reached voltage Interval time 50 ms Measurement interval Scan rate 100 mv/s Voltage sweep rate Range uA Measurement voltage range
[0186] (3) Measurement 1
[0187] A surface of the working electrode was modified with a probe and 6-Hydroxy-1-hexanethiol (HHT) (FIG. 4). In this state, the surface of the working electrode is not charged. Therefore, in the measurement solution, hexacyanoferrate (II) ions (hereinafter referred to as a marker) can reach the surface of the working electrode according to a set potential (FIG. 5). A measured waveform by CV in this state was taken as a basic value (FIG. 6). In addition, a voltage value at which the maximum current value i1 was recorded in the measurement 1 is set to V1.
[0188] (4) Measurement 2: Non-Target Nucleic Acid
[0189] An electrode was modified with a sample containing a non-target nucleic acid (hereinafter, non-complementary electrode). The marker reached a surface of the electrode as in the initial state (FIG. 5), because the non-target nucleic acid hardly hybridized with the probe. Therefore, the same CV waveform (FIG. 7) as in measurement 1 was obtained in measurement 2. A current value i2 at voltage value v1 at which the maximum current value i1 was recorded in measurement 1 is theoretically the same value as the maximum current value i1 in measurement 1 when measurement errors are excluded.
[0190] (5) Measurement 2: Target Nucleic Acid
[0191] Next, an electrode was modified with a sample containing a target nucleic acid (hereinafter, complementary electrode). Because the probe and target nucleic acid hybridized, the marker received repulsion due to a negative charge of the nucleic acid, and therefore it was difficult for the marker to reach the surface of the electrode (FIG. 8). Therefore, in the CV waveform obtained, the current value i2 at the voltage value V1 at which the maximum current value i1 was recorded in measurement 1 decreased (FIG. 9).
[0192] (6) Determination of Hybridization Determination Method
[0193] Based on the above results, whether the measured electrode was a complementary electrode or a non-complementary electrode was determined from a current value at the voltage value V1 at which the maximum current value i1 was recorded in measurement 1. A current value ratio i2/i1 obtained in measurements 1 and 2 is ideally 1 for a case of non-complementary electrodes, and is smaller than 1 for a case of complementary electrodes. Practically, in consideration of measurement error, an electrode was determined to be a non-complementary electrode when a current value ratio was i2/i1.gtoreq.0.9, and was determined to be a complementary electrode when a current value ratio was i2/i1<0.9.
Example 5
Evaluation of Influence on Nucleic Acid Detection by Abasic Site of GC Contiguous Sequence of Probe
[0194] Using the CV measurement method described above, measurements of hybridization of probes 1 to 4 with respect to the following target sequence and non-target sequences were performed.
TABLE-US-00006 (SEQ ID NO: 971) Target sequence: AAAAGCUGGGUUGAGAGGGCGA (SEQ ID NO: 972) Non-target sequence: UGGCAGGGAGGCUGGGAGGGG (Probe) (SEQ ID NO: 967) Probe 1: TCGCCCTCTCAACCCAGCTTTT-Linker (SEQ ID NO: 968) Probe 2: TCGCCCTCTCAAC*CAGCTTTT-Linker (SEQ ID NO: 969) Probe 3: TCGC*CTCTCAACCCAGCTTTT-Linker (SEQ ID NO: 970) Probe 4: TCGC*CTCTCAAC*CAGCTTTT-Linker
[0195] FIG. 10 shows a CV waveform when each of target sequences and non-target sequences is modified for each of probes. The CV waveform of measurement 1 is shown by a dotted line, and the CV waveform of measurement 2 is shown by a solid line, and the current value ratio is described at the upper left.
[0196] Target sequence and probes 1 to 4: Because all current value ratios of measurement 2 to measurement 1 decreased to 0.1 or less, hybridization was correctly performed with the target sequence.
[0197] Non-target sequence and probe 1: A current value ratio is 0.3, and mishybridization with the non-target sequence was caused.
[0198] Non-target sequence and probes 2 and 3: Current ratios are 0.4 and 0.7, which are higher than the current ratio of probe 1 which is 0.3, and therefore the effect of reducing mishybridization by making one site of the GC contiguous sequence abasic was observed.
[0199] Non-target sequence and probe 4: A current value ratio was 0.9 and did not cause mishybridization. The effect obtained by making two sites of the GC contiguous sequence abasic was observed.
Example 6
Evaluation of Influence on Nucleic Acid Detection by Cleavage of GC Contiguous Sequence of Probe
[0200] Using the CV measurement method described above, measurements of hybridization of probes 1 to 4 with respect to the following target sequence and non-target sequences were performed.
TABLE-US-00007 (SEQ ID NO: 973) Target sequence: AGCUACAUUGUCUGCUGGGUUUC (SEQ ID NO: 974) Non-target sequence: UGGCAGGGAGGCUGGGAGGGG (Probe) (SEQ ID NO: 975) Probe 23-mer: GAAACCCAGCGACAATGTAGCT-Linker (SEQ ID NO: 976) Probe 18-mer: CCAGCAGACAATGTAGCT-Linker (SEQ ID NO: 977) Probe 17-mer: CAGCAGACAATGTAGCT-Linker
[0201] FIG. 11 shows a CV waveform when each of target sequences and non-target sequences is modified for each of probes. The CV waveform of measurement 1 is shown by a dotted line, and the CV waveform of measurement 2 is shown by a solid line, and the current value ratio is described at the upper left.
[0202] Target sequence and probe 23-mer: A current value ratio decreased to 0.0, and hybridization occurred correctly with the target sequence.
[0203] Target sequence and probe 18-mer and probe 17-mer: As the chain length decreases, the current value ratio increases, but the ratio is suppressed to 0.2. This means that the hybridization with the target sequence is reduced as compared with the full length, but the current value ratio is sufficiently reduced for the complementation determination.
[0204] Non-target sequence and probe 23-mer: A current value ratio is 0.7, and mishybridization with the non-target sequence was caused.
[0205] Non-target sequence and probe 18-mer and probe 17-mer: A current value ratio was 1.0, and mishybridization was completely suppressed. The effect obtained by cleaving the GC contiguous sequence so that the GC contiguous sequence has less than 3 consecutive bases is observed.
SEQUENCE LISTING
[0206] TN17G016PC ST25.txt
Sequence CWU
1
1
97717DNAArtificial SequenceGC continued sequence 1ggggggg
727DNAArtificial SequenceGC
continued sequence 2ccccccc
736DNAArtificial SequenceGC continued sequence 3gggggg
646DNAArtificial SequenceGC continued sequence 4cccccc
655DNAArtificial SequenceGC
continued sequence 5ggggg
565DNAArtificial SequenceGC continued sequence 6ccccc
574DNAArtificial SequenceGC continued sequence 7gggg
484DNAArtificial SequenceGC
continued sequence 8cccc
493DNAArtificial SequenceGC continued sequence 9ggg
3103DNAArtificial SequenceGC continued sequence 10ccc
3117DNAArtificial
SequenceSubstituted/abasic GC continuous sequencemisc_feature(2)..(2)"n"
is abasic or substituted basemisc_feature(5)..(5)"n" is abasic or
substituted base 11gnggngg
7127DNAArtificial SequenceSubstituted/abasic GC
continuous sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 12ggngngg
7137DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 13ggnggng
7147DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 14ngngngg
7157DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 15ngnggng
7167DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 16nggngng
7177DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(7)..(7)"n" is abasic or substituted base 17nggnggn
7187DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 18gngngng
7197DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted
basemisc_feature(7)..(7)"n" is abasic or substituted base 19gnggngn
7207DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(7)..(7)"n" is abasic or substituted base 20gngnggn
7217DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted
basemisc_feature(7)..(7)"n" is abasic or substituted base 21ggngngn
7227DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 22cnccncc
7237DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 23ccncncc
7247DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 24ccnccnc
7257DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 25ncncncc
7267DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 26ncnccnc
7277DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 27nccncnc
7287DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(7)..(7)"n" is abasic or substituted base 28nccnccn
7297DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 29cncncnc
7307DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(7)..(7)"n" is abasic or substituted base 30cncnccn
7317DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted
basemisc_feature(7)..(7)"n" is abasic or substituted base 31cnccncn
7327DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted
basemisc_feature(7)..(7)"n" is abasic or substituted base 32ccncncn
7336DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 33nggngg
6346DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 34gngngg
6356DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 35gnggng
6366DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 36ggngng
6376DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 37ggnggn
6386DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 38ngngng
6396DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 39ngnggn
6406DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 40nggngn
6416DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 41gngngn
6426DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 42nccncc
6436DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 43cncncc
6446DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 44cnccnc
6456DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 45ccncnc
6466DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 46ccnccn
6476DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 47ncncnc
6486DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 48ncnccn
6496DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 49nccncn
6506DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted
basemisc_feature(6)..(6)"n" is abasic or substituted base 50cncncn
6515DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted base 51ggngg
5525DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted base 52ngngg
5535DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 53nggng
5545DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 54gngng
5555DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 55gnggn
5565DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 56ggngn
5575DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted base 57ccncc
5585DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted base 58ncncc
5595DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 59nccnc
5605DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 60cncnc
5615DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 61cnccn
5625DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted
basemisc_feature(5)..(5)"n" is abasic or substituted base 62ccncn
5634DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted base 63gngg
4644DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted base 64ggng
4654DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted base 65ngng
4664DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 66nggn
4674DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 67gngn
4684DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted base 68cncc
4694DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted base 69ccnc
4704DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted base 70ncnc
4714DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 71nccn
4724DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted
basemisc_feature(4)..(4)"n" is abasic or substituted base 72cncn
4733DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted base 73ngg
3743DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted base 74gng
3753DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted base 75ggn
3763DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted
basemisc_feature(3)..(3)"n" is abasic or substituted base 76ngn
3773DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)"n" is abasic or substituted base 77ncc
3783DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(2)..(2)"n" is abasic or substituted base 78cnc
3793DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(3)..(3)"n" is abasic or substituted base 79ccn
3803DNAArtificial SequenceSubstituted/abasic GC continuous
sequencemisc_feature(1)..(1)n is abasic or substituted
basemisc_feature(3)..(3)n is abasic or substituted base 80ncn
38115RNAHomo
sapiens 81aggagauccu ggguu
158216RNAHomo sapiens 82cucuccuccc ggcuuc
168316RNAHomo sapiens 83gcagcauuca uguccc
168416RNAHomo sapiens
84aggaaacagg gaccca
168517RNAHomo sapiens 85ucgccuccuc cucuccc
178617RNAHomo sapiens 86gggauaugaa gaaaaau
178717RNAHomo sapiens
87ccugagaaaa gggccaa
178817RNAHomo sapiens 88augugggcuc aggcuca
178917RNAHomo sapiens 89ccggcauguc cagggca
179017RNAHomo sapiens
90acauugccag ggaguuu
179117RNAHomo sapiens 91cacugugggu acaugcu
179217RNAHomo sapiens 92ucccugagca aagccac
179317RNAHomo sapiens
93ccaguuuucc caggauu
179417RNAHomo sapiens 94ugagggagga gacugca
179517RNAHomo sapiens 95acagggagga gauugua
179617RNAHomo sapiens
96gccggacaag agggagg
179717RNAHomo sapiens 97uuggaggcgu ggguuuu
179817RNAHomo sapiens 98agggugugug uguuuuu
179917RNAHomo sapiens
99ggagugggcu ggugguu
1710017RNAHomo sapiens 100gcugggcgag gcuggca
1710117RNAHomo sapiens 101aagacugaga ggaggga
1710217RNAHomo sapiens
102guggaccugg cugggac
1710317RNAHomo sapiens 103ucccuguucg ggcgcca
1710417RNAHomo sapiens 104ucccaccgcu gccaccc
1710517RNAHomo sapiens
105gggagucuac agcaggg
1710617RNAHomo sapiens 106cuccgggacg gcugggc
1710717RNAHomo sapiens 107cgcgccgggc ccggguu
1710818RNAHomo sapiens
108ucagcuggcc cucauuuc
1810918RNAHomo sapiens 109aucccaccuc ugccacca
1811018RNAHomo sapiens 110gucccuguuc aggcgcca
1811118RNAHomo sapiens
111gcaugggugg uucagugg
1811218RNAHomo sapiens 112cagggaggug aaugugau
1811318RNAHomo sapiens 113uccagugccc uccucucc
1811418RNAHomo sapiens
114ccaggcucug caguggga
1811518RNAHomo sapiens 115ugggagcugg acuacuuc
1811618RNAHomo sapiens 116ucccuggagu uucuucuu
1811718RNAHomo sapiens
117gggauucugu agcuuccu
1811818RNAHomo sapiens 118cagcagugcg cagggcug
1811918RNAHomo sapiens 119auggucaccu ccgggacu
1812018RNAHomo sapiens
120aggagaaguc gggaaggu
1812118RNAHomo sapiens 121gugaaggccc ggcggaga
1812218RNAHomo sapiens 122gcgugugcuu gcuguggg
1812318RNAHomo sapiens
123cucugggaaa ugggacag
1812418RNAHomo sapiens 124aggcugggcu gggacgga
1812518RNAHomo sapiens 125cccagcagga cgggagcg
1812618RNAHomo sapiens
126gggugagggc aggugguu
1812718RNAHomo sapiens 127ggugggcuuc ccggaggg
1812819RNAHomo sapiens 128gugaggacuc gggaggugg
1912919RNAHomo sapiens
129uggauuuuug gaucaggga
1913019RNAHomo sapiens 130acuggccugg gacuaccgg
1913119RNAHomo sapiens 131agggaccuga gugucuaag
1913219RNAHomo sapiens
132gcauugugca gggcuauca
1913319RNAHomo sapiens 133ccugagaccc uaguuccac
1913419RNAHomo sapiens 134agagcuggcu gaagggcag
1913519RNAHomo sapiens
135aggcagguua ucugggcug
1913619RNAHomo sapiens 136aagucccacu aaugccagc
1913719RNAHomo sapiens 137ugggcguauc uguaugcua
1913819RNAHomo sapiens
138ccgguuccag ucccuggag
1913919RNAHomo sapiens 139ugagggagug gauuguaug
1914019RNAHomo sapiens 140ggcuggucag augggagug
1914119RNAHomo sapiens
141gugucugcuu ccuguggga
1914219RNAHomo sapiens 142aagugugcag ggcacuggu
1914319RNAHomo sapiens 143aguuuucccu ucaagucaa
1914419RNAHomo sapiens
144cauucucguu uccuucccu
1914519RNAHomo sapiens 145gagggcgggu ggaggagga
1914619RNAHomo sapiens 146aucgggcccu cggcgccgg
1914719RNAHomo sapiens
147cugugggcuc agcucuggg
1914819RNAHomo sapiens 148ucucccuuga gggcacuuu
1914919RNAHomo sapiens 149ugcccuccuu ucuucccuc
1915019RNAHomo sapiens
150ucuagugcgg gcguucccg
1915119RNAHomo sapiens 151ugagggaguu ggguguaua
1915219RNAHomo sapiens 152ugagggagga gguugggua
1915319RNAHomo sapiens
153ugagggagug ggugggagg
1915419RNAHomo sapiens 154ugucccucug ggucgccca
1915520RNAHomo sapiens 155ucugcagggu uugcuuugag
2015620RNAHomo sapiens
156gugucugggc ggacagcugc
2015720RNAHomo sapiens 157uaaagagccc uguggagaca
2015820RNAHomo sapiens 158ccuccugccc uccuugcugu
2015920RNAHomo sapiens
159auauggguuu acuaguuggu
2016020RNAHomo sapiens 160aggcauggga ggucagguga
2016120RNAHomo sapiens 161gcucggacug agcagguggg
2016220RNAHomo sapiens
162ucccacuacu ucacuuguga
2016320RNAHomo sapiens 163uguuccucug ucucccagac
2016420RNAHomo sapiens 164aaaagcuggg cugagaggcg
2016520RNAHomo sapiens
165uaacggccgc gguacccuaa
2016620RNAHomo sapiens 166aaaugggugg ucugaggcaa
2016720RNAHomo sapiens 167ugaggagaug cugggacuga
2016820RNAHomo sapiens
168ccauggaucu ccaggugggu
2016920RNAHomo sapiens 169guccgcucgg cgguggccca
2017020RNAHomo sapiens 170agaccauggg uucucauugu
2017120RNAHomo sapiens
171cuuauaucag aggcuguggg
2017220RNAHomo sapiens 172aggguguuuc ucucaucucu
2017320RNAHomo sapiens 173aggcgcaccc gaccacaugc
2017420RNAHomo sapiens
174guagaggaga uggcgcaggg
2017520RNAHomo sapiens 175gaauugauca ggacauaggg
2017620RNAHomo sapiens 176ugagcccugu ccucccgcag
2017720RNAHomo sapiens
177agagguauag ggcaugggaa
2017820RNAHomo sapiens 178ccucugggcc cuuccuccag
2017920RNAHomo sapiens 179cccugagacc cuaaccuuaa
2018020RNAHomo sapiens
180ugugggacug caaaugggag
2018120RNAHomo sapiens 181augggugaug gguguggugu
2018220RNAHomo sapiens 182ggagguuggg aagggcagag
2018320RNAHomo sapiens
183ucucccuuca ugugcccaga
2018420RNAHomo sapiens 184cuggguuggg cugggcuggg
2018521RNAHomo sapiens 185gcagagcugc agaugggauu c
2118621RNAHomo sapiens
186uugcucacug uucuucccua g
2118721RNAHomo sapiens 187ccgucgccgc cacccgagcc g
2118821RNAHomo sapiens 188agaggauacc cuuuguaugu u
2118921RNAHomo sapiens
189cccggagcca ggaugcagcu c
2119021RNAHomo sapiens 190agugaaugau ggguucugac c
2119121RNAHomo sapiens 191ugcaggacca agaugagccc u
2119221RNAHomo sapiens
192uggacugccc ugaucuggag a
2119321RNAHomo sapiens 193uuaggccgca gaucugggug a
2119421RNAHomo sapiens 194cuuuuugcgg ucugggcuug c
2119521RNAHomo sapiens
195uugggacaua cuuaugcuaa a
2119621RNAHomo sapiens 196uugggacaua cuuaugcuaa a
2119721RNAHomo sapiens 197uugggacaua cuuaugcuaa a
2119821RNAHomo sapiens
198uugggacaua cuuaugcuaa a
2119921RNAHomo sapiens 199uugggacaua cuuaugcuaa a
2120021RNAHomo sapiens 200acucuuuccc uguugcacua c
2120121RNAHomo sapiens
201uaccacaggg uagaaccacg g
2120221RNAHomo sapiens 202ugagugccgg ugccugcccu g
2120321RNAHomo sapiens 203ugauauguuu gauauugggu u
2120421RNAHomo sapiens
204caacaccagu cgaugggcug u
2120521RNAHomo sapiens 205cgagccucaa gcaagggacu u
2120621RNAHomo sapiens 206agcuacaucu ggcuacuggg u
2120721RNAHomo sapiens
207ugacagcgcc cugccuggcu c
2120821RNAHomo sapiens 208aucacauugc cagggauuuc c
2120921RNAHomo sapiens 209aucacauugc cagggauuac c
2121021RNAHomo sapiens
210aggcggagac uugggcaauu g
2121121RNAHomo sapiens 211guuagggcca acaucucuug g
2121221RNAHomo sapiens 212uucgcgggcg aaggcaaagu c
2121321RNAHomo sapiens
213gcugcaccgg agacugggua a
2121421RNAHomo sapiens 214uacccagucu ccggugcagc c
2121521RNAHomo sapiens 215ccaggcucug cagugggaac u
2121621RNAHomo sapiens
216cucccacuuc cagaucuuuc u
2121721RNAHomo sapiens 217ccugcagaga ggaagcccuu c
2121821RNAHomo sapiens 218ggccagccac caggagggcu g
2121921RNAHomo sapiens
219ucaccugagc ucccgugccu g
2122021RNAHomo sapiens 220ugugucccau uauuggugau u
2122121RNAHomo sapiens 221ugaguguugu cuacgagggc a
2122221RNAHomo sapiens
222acagggccgc agauggagac u
2122321RNAHomo sapiens 223gcaggcacag acagcccugg c
2122421RNAHomo sapiens 224uuagcggugg accgcccugc g
2122521RNAHomo sapiens
225aaaagcauca ggaaguaccc a
2122621RNAHomo sapiens 226gaccgagagg gccucggcug u
2122721RNAHomo sapiens 227auuggacugc ugauggcccg u
2122821RNAHomo sapiens
228gcaguccaug ggcauauaca c
2122921RNAHomo sapiens 229ucuugaaguc agaacccgca a
2123021RNAHomo sapiens 230gcagcccagc ugaggccucu g
2123121RNAHomo sapiens
231acacaugggu ggcuguggcc u
2123221RNAHomo sapiens 232gcccugaccu guccuguucu g
2123321RNAHomo sapiens 233agcggugcuc cugcgggccg a
2123421RNAHomo sapiens
234gagggcaugc gcacuuuguc c
2123521RNAHomo sapiens 235ugcuuaaccu ugcccucgaa a
2123621RNAHomo sapiens 236ucacuccucu ccucccgucu u
2123721RNAHomo sapiens
237cccagauaau ggcacucuca a
2123821RNAHomo sapiens 238uuucccuuuc cauccuggca g
2123921RNAHomo sapiens 239uugccagggc aggaggugga a
2124021RNAHomo sapiens
240auccuugcua ucugggugcu a
2124121RNAHomo sapiens 241uaaggcaccc uucugaguag a
2124221RNAHomo sapiens 242gugggauuuc ugaguagcau c
2124321RNAHomo sapiens
243caauucucaa aggagccucc c
2124421RNAHomo sapiens 244acuggcauua gugggacuuu u
2124521RNAHomo sapiens 245ggcugggugc ucuugugcag u
2124621RNAHomo sapiens
246cagaucaugg gacugucuca g
2124721RNAHomo sapiens 247caaagaggaa ggucccauua c
2124821RNAHomo sapiens 248uuggccacaa uggguuagaa c
2124921RNAHomo sapiens
249acggcccagg cggcauuggu g
2125021RNAHomo sapiens 250gggaagagcu guacggccuu c
2125121RNAHomo sapiens 251ugagcuaaau gugugcuggg a
2125221RNAHomo sapiens
252agaccuggcc cagaccucag c
2125321RNAHomo sapiens 253acacuuguug ggaugaccug c
2125421RNAHomo sapiens 254gggacuagga ugcagaccuc c
2125521RNAHomo sapiens
255gaagaauagg agggacuuug u
2125621RNAHomo sapiens 256ucuagaaaug caugacccac c
2125721RNAHomo sapiens 257ucaaguguca ucugucccua g
2125821RNAHomo sapiens
258uuggagggug uggaagacau c
2125921RNAHomo sapiens 259aauggcgcca cuaggguugu g
2126021RNAHomo sapiens 260uccgguucuc agggcuccac c
2126121RNAHomo sapiens
261uaguggucag agggcuuaug a
2126221RNAHomo sapiens 262cacgcgggaa ccgaguccac c
2126321RNAHomo sapiens 263cgacgagggc cggucggucg c
2126421RNAHomo sapiens
264ucacccuucc auaucuaguc u
2126521RNAHomo sapiens 265uccugcgcgu cccagaugcc c
2126621RNAHomo sapiens 266cucccacaug caggguuugc a
2126721RNAHomo sapiens
267caucccuugc augguggagg g
2126821RNAHomo sapiens 268ccucccaugc caagaacucc c
2126921RNAHomo sapiens 269ugggcucagg guacaaaggu u
2127021RNAHomo sapiens
270cugggcucgg gacgcgcggc u
2127121RNAHomo sapiens 271agacccugca gccuucccac c
2127221RNAHomo sapiens 272cgccugccca gcccuccugc u
2127321RNAHomo sapiens
273ccugugcucc cagggccucg c
2127421RNAHomo sapiens 274ucauccucgu cucccuccca g
2127521RNAHomo sapiens 275auacccauag cuuagcuccc a
2127621RNAHomo sapiens
276ugggagcuaa gcuaugggua u
2127721RNAHomo sapiens 277aagccugccc ggcuccucgg g
2127821RNAHomo sapiens 278uggguuuacg uugggagaac u
2127921RNAHomo sapiens
279ucccacguug uggcccagca g
2128021RNAHomo sapiens 280cgcgggugcu uacugacccu u
2128121RNAHomo sapiens 281cuccuucacc cgggcgguac c
2128221RNAHomo sapiens
282cuuccgcccg gccggguguc g
2128321RNAHomo sapiens 283auugucccuc ucccuuccca g
2128421RNAHomo sapiens 284ggcgcgccca gcucccgggc u
2128522RNAHomo sapiens
285cuauacaacc uacugccuuc cc
2228622RNAHomo sapiens 286cuauacaauc uauugccuuc cc
2228722RNAHomo sapiens 287aacccguaga uccgaacuug ug
2228822RNAHomo sapiens
288ccgcacugug gguacuugcu gc
2228922RNAHomo sapiens 289uuuccggcuc gcgugggugu gu
2229022RNAHomo sapiens 290acaggugagg uucuugggag cc
2229122RNAHomo sapiens
291ucacaaguca ggcucuuggg ac
2229222RNAHomo sapiens 292augggugaau uuguagaagg au
2229322RNAHomo sapiens 293augguacccu ggcauacuga gu
2229422RNAHomo sapiens
294cugaagcuca gagggcucug au
2229522RNAHomo sapiens 295ucuauacaga cccuggcuuu uc
2229622RNAHomo sapiens 296ucugggcaac aaagugagac cu
2229722RNAHomo sapiens
297uggguggucu ggagauuugu gc
2229822RNAHomo sapiens 298uucuggaauu cugugugagg ga
2229922RNAHomo sapiens 299uuuucaacuc uaaugggaga ga
2230022RNAHomo sapiens
300cagugcaaug uuaaaagggc au
2230122RNAHomo sapiens 301cagugcaaug augaaagggc au
2230222RNAHomo sapiens 302uauagggauu ggagccgugg cg
2230322RNAHomo sapiens
303gcuacuucac aacaccaggg cc
2230422RNAHomo sapiens 304gcuauuucac gacaccaggg uu
2230522RNAHomo sapiens 305ggagacgcgg cccuguugga gu
2230622RNAHomo sapiens
306cagugguuuu acccuauggu ag
2230722RNAHomo sapiens 307ugagaacuga auuccauggg uu
2230822RNAHomo sapiens 308ugcccugugg acucaguucu gg
2230922RNAHomo sapiens
309gcccgcgugu ggagccaggu gu
2231022RNAHomo sapiens 310gugaauuacc gaagggccau aa
2231122RNAHomo sapiens 311uggacggaga acugauaagg gu
2231222RNAHomo sapiens
312caaagaauuc uccuuuuggg cu
2231322RNAHomo sapiens 313uacccagagc augcagugug aa
2231422RNAHomo sapiens 314aacuggccua caaaguccca gu
2231522RNAHomo sapiens
315uagguaguuu cauguuguug gg
2231622RNAHomo sapiens 316uagguaguuu ccuguuguug gg
2231722RNAHomo sapiens 317uucaccaccu ucuccaccca gc
2231822RNAHomo sapiens
318gauuagggug cuuagcuguu aa
2231922RNAHomo sapiens 319cucccacugc uucacuugac ua
2232022RNAHomo sapiens 320caucuuacug ggcagcauug ga
2232122RNAHomo sapiens
321cgucuuaccc agcaguguuu gg
2232222RNAHomo sapiens 322uucccuuugu cauccuaugc cu
2232322RNAHomo sapiens 323acuguaguau gggcacuucc ag
2232422RNAHomo sapiens
324uucccuuugu cauccuucgc cu
2232522RNAHomo sapiens 325uagucccuuc cuugaagcgg uc
2232622RNAHomo sapiens 326agaguugagu cuggacgucc cg
2232722RNAHomo sapiens
327acacagggcu guugugaaga cu
2232822RNAHomo sapiens 328uggguuccug gcaugcugau uu
2232922RNAHomo sapiens 329agggcuuagc ugcuugugag ca
2233022RNAHomo sapiens
330uaugugggau gguaaaccgc uu
2233122RNAHomo sapiens 331ugguuuaccg ucccacauac au
2233222RNAHomo sapiens 332uauacaaggg cagacucucu cu
2233322RNAHomo sapiens
333cugggaggug gauguuuacu uc
2233422RNAHomo sapiens 334cugggagaag gcuguuuacu cu
2233522RNAHomo sapiens 335ugccuggaac auaguaggga cu
2233622RNAHomo sapiens
336guugggacaa gaggacgguc uu
2233722RNAHomo sapiens 337acuuuccuca cucccgugaa gu
2233822RNAHomo sapiens 338ugagggacag augccagaag ca
2233922RNAHomo sapiens
339uaaagaacuc uuaaaaccca au
2234022RNAHomo sapiens 340uggcccaacc uauucaguua gu
2234122RNAHomo sapiens 341agcuuuuggg aauucaggua gu
2234222RNAHomo sapiens
342aaagaucugg aagugggaga ca
2234322RNAHomo sapiens 343cugcccuagu cuagcugaag cu
2234422RNAHomo sapiens 344aagggcuucc ucucugcagg ac
2234522RNAHomo sapiens
345agagcugaga cuagaaagcc ca
2234622RNAHomo sapiens 346uauaaaauga gggcaguaag ac
2234722RNAHomo sapiens 347ugugacuuua agggaaaugg cg
2234822RNAHomo sapiens
348ugcccugccu guuuucuccu uu
2234922RNAHomo sapiens 349uggaagggag aagagcuuua au
2235022RNAHomo sapiens 350ucucugggcc ugugucuuag gc
2235122RNAHomo sapiens
351cagugccucg gcagugcagc cc
2235222RNAHomo sapiens 352gcugacuccu aguccagggc uc
2235322RNAHomo sapiens 353caaucagcaa guauacugcc cu
2235422RNAHomo sapiens
354agguagacug ggauuuguug uu
2235522RNAHomo sapiens 355aaagacauag uugcaagaug gg
2235622RNAHomo sapiens 356gggaccaucc ugccugcugu gg
2235722RNAHomo sapiens
357ucaccugacc ucccaugccu gu
2235822RNAHomo sapiens 358caggcacggg agcucaggug ag
2235922RNAHomo sapiens 359cggguggauc acgaugcaau uu
2236022RNAHomo sapiens
360ugaccuggga cucggacagc ug
2236122RNAHomo sapiens 361accuuccucu ccaugggucu uu
2236222RNAHomo sapiens 362aaagacccau ugaggagaag gu
2236322RNAHomo sapiens
363cucgugggcu cuggccacgg cc
2236422RNAHomo sapiens 364caguggccag agcccugcag ug
2236522RNAHomo sapiens 365uuuccuaccc uaccugaaga cu
2236622RNAHomo sapiens
366cugggaggug ugauaucgug gu
2236722RNAHomo sapiens 367ugugauauca ugguuccugg ga
2236822RNAHomo sapiens 368cugggaggug ugauauugug gu
2236922RNAHomo sapiens
369ugugauauca ugguuccugg ga
2237022RNAHomo sapiens 370cugggaggug ugauauugug gu
2237122RNAHomo sapiens 371gggaggugug aucucacacu cg
2237222RNAHomo sapiens
372ugugauauca ugguuccugg ga
2237322RNAHomo sapiens 373ugugauaucg ugcuuccugg ga
2237422RNAHomo sapiens 374agagguugcc cuuggugaau uc
2237522RNAHomo sapiens
375uauacaaggg caagcucucu gu
2237622RNAHomo sapiens 376uguccucuag ggccugcagu cu
2237722RNAHomo sapiens 377agacaucaag aucaguccca aa
2237822RNAHomo sapiens
378uuugggacug aucuugaugu cu
2237922RNAHomo sapiens 379aacuaguaau guuggauuag gg
2238022RNAHomo sapiens 380ugcucagguu gcacagcugg ga
2238122RNAHomo sapiens
381acuggacuua gggucagaag gc
2238222RNAHomo sapiens 382cugggacagg aggaggaggc ag
2238322RNAHomo sapiens 383caggucgucu ugcagggcuu cu
2238422RNAHomo sapiens
384aucaugaugg gcuccucggu gu
2238522RNAHomo sapiens 385aguugccuuu uuguucccau gc
2238622RNAHomo sapiens 386uguugggauu cagcaggacc au
2238722RNAHomo sapiens
387caaggagacg ggaacaugga gc
2238822RNAHomo sapiens 388cagggcagga agaaguggac aa
2238922RNAHomo sapiens 389guccacuucu gccugcccug cc
2239022RNAHomo sapiens
390uggcggcggu aguuaugggc uu
2239122RNAHomo sapiens 391ugggaacuua guagagguuu aa
2239222RNAHomo sapiens 392caagggacca agcauucauu au
2239322RNAHomo sapiens
393caggaaggau uuagggacag gc
2239422RNAHomo sapiens 394uugcauaugu aggauguccc au
2239522RNAHomo sapiens 395ucugguaaga gauuugggca ua
2239622RNAHomo sapiens
396gaggaaacug aagcugagag gg
2239722RNAHomo sapiens 397uugggaucau uuugcaucca ua
2239822RNAHomo sapiens 398ugagggagua ggauguaugg uu
2239922RNAHomo sapiens
399gaagaacugu ugcauuugcc cu
2240022RNAHomo sapiens 400agacugacgg cuggaggccc au
2240122RNAHomo sapiens 401gcugacagca gggcuggccg cu
2240222RNAHomo sapiens
402gagcuuggau gagcugggcu ga
2240322RNAHomo sapiens 403acccuaucaa uauugucucu gc
2240422RNAHomo sapiens 404ugccgcccuc ucgcugcucu ag
2240522RNAHomo sapiens
405ugugggaucu ggaggcaucu gg
2240622RNAHomo sapiens 406uguguccggg aaguggagga gg
2240722RNAHomo sapiens 407aacgggaaug caggcuguau cu
2240822RNAHomo sapiens
408gagcaggcga ggcugggcug aa
2240922RNAHomo sapiens 409ucaggcagug uggguaucag au
2241022RNAHomo sapiens 410caggaggcag ugggcgagca gg
2241122RNAHomo sapiens
411uaggccacag ccacccaugu gu
2241222RNAHomo sapiens 412ugagggcucc aggugacggu gg
2241322RNAHomo sapiens 413accugccagc accucccugc ag
2241422RNAHomo sapiens
414auagugggaa gcuggcagau uc
2241522RNAHomo sapiens 415ucauuuaucu guugggaagc ua
2241622RNAHomo sapiens 416ccaccagguc uagcauuggg au
2241722RNAHomo sapiens
417aggacugauc cucucgggca gg
2241822RNAHomo sapiens 418agggaaggag gcuuggucuu ag
2241922RNAHomo sapiens 419cucgggcgga ggugguugag ug
2242022RNAHomo sapiens
420agccaggcuc ugaagggaaa gu
2242122RNAHomo sapiens 421uuucccuuca gagccuggcu uu
2242222RNAHomo sapiens 422uuaacuccuu ucacacccau gg
2242322RNAHomo sapiens
423auucucucug gaucccaugg au
2242422RNAHomo sapiens 424guggaccagg auggcaaggg cu
2242522RNAHomo sapiens 425uaggagggaa uaguaaaagc ag
2242622RNAHomo sapiens
426ugaagccagc ucuggucugg gc
2242722RNAHomo sapiens 427uuacggacca gcuaagggag gc
2242822RNAHomo sapiens 428aaucauacag ggacauccag uu
2242922RNAHomo sapiens
429aaucguacag ggucauccac uu
2243022RNAHomo sapiens 430cuuaugcaag auucccuucu ac
2243122RNAHomo sapiens 431ugaaacauac acgggaaacc uc
2243222RNAHomo sapiens
432augcaccugg gcaaggauuc ug
2243322RNAHomo sapiens 433cuuggauuuu ccugggccuc ag
2243422RNAHomo sapiens 434ugaggacagg gcaaauucac ga
2243522RNAHomo sapiens
435aaugcaccug ggcaaggauu ca
2243622RNAHomo sapiens 436agacccuggu cugcacucua uc
2243722RNAHomo sapiens 437gggagccagg aaguauugau gu
2243822RNAHomo sapiens
438ugauugguac gucugugggu ag
2243922RNAHomo sapiens 439uucagauccc agcggugccu cu
2244022RNAHomo sapiens 440uccuccucua ccucauccca gu
2244122RNAHomo sapiens
441gaauaugggu auauuaguuu gg
2244222RNAHomo sapiens 442aaacuaauau acccauauuc ug
2244322RNAHomo sapiens 443cugaauagcu gggacuacag gu
2244422RNAHomo sapiens
444agaaagggug gcaauaccuc uu
2244522RNAHomo sapiens 445agguauugcc acccuuucua gu
2244622RNAHomo sapiens 446uuagaacguu uuagggucaa au
2244722RNAHomo sapiens
447caaauaauac cacagugggu gu
2244822RNAHomo sapiens 448ugagucagca acauauccca ug
2244922RNAHomo sapiens 449uuaggccauc aucccauuau gc
2245022RNAHomo sapiens
450cacgcucaug cacacaccca ca
2245122RNAHomo sapiens 451uuaugguuug ccugggacug ag
2245222RNAHomo sapiens 452agucauugga ggguuugagc ag
2245322RNAHomo sapiens
453acucaaaacc cuucagugac uu
2245422RNAHomo sapiens 454agacuuccca uuugaaggug gc
2245522RNAHomo sapiens 455aguauucugu accagggaag gu
2245622RNAHomo sapiens
456gucccucucc aaaugugucu ug
2245722RNAHomo sapiens 457agcaguguuu guuuugccca ca
2245822RNAHomo sapiens 458ucgggcgcaa gagcacugca gu
2245922RNAHomo sapiens
459aguugccagg gcugccuuug gu
2246022RNAHomo sapiens 460caaaguccuu ccuauuuuuc cc
2246122RNAHomo sapiens 461ugggccaugc auuucuagaa cu
2246222RNAHomo sapiens
462ccucaccauc ccuucugccu gc
2246322RNAHomo sapiens 463uuccagcccu ucuaauggua gg
2246422RNAHomo sapiens 464uggugggccg cagaacaugu gc
2246522RNAHomo sapiens
465uacccauugc auaucggagu ug
2246622RNAHomo sapiens 466gcacugagau gggaguggug ua
2246722RNAHomo sapiens 467caacaaaucc cagucuaccu aa
2246822RNAHomo sapiens
468ugagaccucu ggguucugag cu
2246922RNAHomo sapiens 469uccauuacac uacccugccu cu
2247022RNAHomo sapiens 470gacugacacc ucuuugggug aa
2247122RNAHomo sapiens
471cacuggcucc uuucugggua ga
2247222RNAHomo sapiens 472uauugcacuu gucccggccu gu
2247322RNAHomo sapiens 473uauugcacuc gucccggccu cc
2247422RNAHomo sapiens
474acugcugagc uagcacuucc cg
2247522RNAHomo sapiens 475acaguagagg gaggaaucgc ag
2247622RNAHomo sapiens 476uucaacgggu auuuauugag ca
2247722RNAHomo sapiens
477aacccguaga uccgaucuug ug
2247822RNAHomo sapiens 478caagcucgcu ucuauggguc ug
2247922RNAHomo sapiens 479cacccguaga accgaccuug cg
2248022RNAHomo sapiens
480caagcucgug ucuguggguc cg
2248122RNAHomo sapiens 481caucaaagug gaggcccucu cu
2248222RNAHomo sapiens 482gaucaaagug gaggcccucu cc
2248322RNAHomo sapiens
483aaagugcuuc ccuuuugugu gu
2248422RNAHomo sapiens 484uucacaaagc ccauacacuu uc
2248522RNAHomo sapiens 485gaucagggcc uuucuaagua ga
2248622RNAHomo sapiens
486agcgggcaca gcugugagag cc
2248722RNAHomo sapiens 487aucccugagu guauguggug aa
2248822RNAHomo sapiens 488auugcuuccc agacggugaa ga
2248922RNAHomo sapiens
489agauugggca uaggugacug aa
2249022RNAHomo sapiens 490agagaaaccc ugucucaaaa aa
2249122RNAHomo sapiens 491gaaagccacc augcugggua aa
2249222RNAHomo sapiens
492gcagcagggu gaaacugaca ca
2249322RNAHomo sapiens 493ccagcuggga agaaccagug gc
2249422RNAHomo sapiens 494gcaugacacc acacugggua ga
2249522RNAHomo sapiens
495uacugagaau ggguagcagu ca
2249622RNAHomo sapiens 496cagcccugcu gucuuaaccu cu
2249722RNAHomo sapiens 497uagaguuaca cccugggagu ua
2249822RNAHomo sapiens
498ucaccagccc uguguucccu ag
2249922RNAHomo sapiens 499ucccugagac ccuaacuugu ga
2250022RNAHomo sapiens 500acggguuagg cucuugggag cu
2250122RNAHomo sapiens
501uuagggcccu ggcuccaucu cc
2250222RNAHomo sapiens 502auguagggcu aaaagccaug gg
2250322RNAHomo sapiens 503ucucccaacc cuuguaccag ug
2250422RNAHomo sapiens
504gcccaaaggu gaauuuuuug gg
2250522RNAHomo sapiens 505ggcuacaaca caggacccgg gc
2250622RNAHomo sapiens 506accuugccuu gcugcccggg cc
2250722RNAHomo sapiens
507ugggucuuug cgggcgagau ga
2250822RNAHomo sapiens 508aacuggcccu caaagucccg cu
2250922RNAHomo sapiens 509gaggguuggg uggaggcucu cc
2251022RNAHomo sapiens
510cugggagagg guuguuuacu cc
2251122RNAHomo sapiens 511aaaagcuggg uugagagggc ga
2251222RNAHomo sapiens 512cuggcccucu cugcccuucc gu
2251322RNAHomo sapiens
513cuagguaugg ucccagggau cc
2251422RNAHomo sapiens 514aaaaugaaau gagcccagcc ca
2251522RNAHomo sapiens 515aauucccuug uagauaaccc gg
2251622RNAHomo sapiens
516aucgggaaug ucguguccgc cc
2251722RNAHomo sapiens 517cagggcuggc agugacaugg gu
2251822RNAHomo sapiens 518auuucccugc cauucccuug gc
2251922RNAHomo sapiens
519gcucccucua gggucgcucg ga
2252022RNAHomo sapiens 520aacccagugg gcuauggaaa ug
2252122RNAHomo sapiens 521ugggcuggca gggcaagugc ug
2252222RNAHomo sapiens
522cagggccuca cuguaucgcc ca
2252322RNAHomo sapiens 523aggacuggac ucccggcagc cc
2252422RNAHomo sapiens 524gcugaacugg gcugagcugg gc
2252522RNAHomo sapiens
525acugggaaga ggagcugagg ga
2252622RNAHomo sapiens 526ucucccuucc ugcccuggcu ag
2252722RNAHomo sapiens 527ugggauccag acagugggag aa
2252822RNAHomo sapiens
528uucucccacu accaggcucc ca
2252922RNAHomo sapiens 529acccagguuc ccucuggccg ca
2253022RNAHomo sapiens 530aaucccaaug cuagacccgg ug
2253122RNAHomo sapiens
531gcugcgggcu gcggucaggg cg
2253222RNAHomo sapiens 532gcccgagagg auccgucccu gc
2253322RNAHomo sapiens 533acccuugagc cugaucccua gc
2253422RNAHomo sapiens
534aagacgggag gaaagaaggg ag
2253522RNAHomo sapiens 535aaugcacccg ggcaaggauu cu
2253622RNAHomo sapiens 536aauccuuugu cccuggguga ga
2253722RNAHomo sapiens
537ugggaugagg gauugaagug ga
2253822RNAHomo sapiens 538uaguucuucc cuuugcccaa uu
2253922RNAHomo sapiens 539cagggaaaug ggaagaacua ga
2254022RNAHomo sapiens
540acagcccagc aguuaucacg gg
2254122RNAHomo sapiens 541uccgagccug ggucucccuc uu
2254222RNAHomo sapiens 542guucucccaa cguaagccca gc
2254322RNAHomo sapiens
543uccucuucuc ccuccuccca gg
2254422RNAHomo sapiens 544gugaacgggc gccaucccga gg
2254522RNAHomo sapiens 545agggacggga cgcggugcag ug
2254622RNAHomo sapiens
546ugugcgcagg gagaccucuc cc
2254722RNAHomo sapiens 547ugcccuuaaa ggugaaccca gu
2254822RNAHomo sapiens 548cccugugccc ggcccacuuc ug
2254922RNAHomo sapiens
549ucacccugca ucccgcaccc ag
2255022RNAHomo sapiens 550cagcccggau cccagcccac uu
2255122RNAHomo sapiens 551cagcccuccu cccgcaccca aa
2255222RNAHomo sapiens
552aaggcccggg cuuuccuccc ag
2255322RNAHomo sapiens 553cugcccuggc ccgagggacc ga
2255422RNAHomo sapiens 554gugggcuggg cugggcuggg cc
2255523RNAHomo sapiens
555agcagcauug uacagggcua uga
2355623RNAHomo sapiens 556agcagcauug uacagggcua uca
2355723RNAHomo sapiens 557uacccuguag auccgaauuu gug
2355823RNAHomo sapiens
558uacccuguag aaccgaauuu gug
2355923RNAHomo sapiens 559ucuggcuccg ugucuucacu ccc
2356023RNAHomo sapiens 560aacauucauu gcugucggug ggu
2356123RNAHomo sapiens
561aacauucauu guugucggug ggu
2356223RNAHomo sapiens 562acugcccuaa gugcuccuuc ugg
2356323RNAHomo sapiens 563caacggaauc ccaaaagcag cug
2356423RNAHomo sapiens
564ugaguaccgc caugucuguu ggg
2356523RNAHomo sapiens 565cccaguguuc agacuaccug uuc
2356623RNAHomo sapiens 566cccaguguuu agacuaucug uuc
2356723RNAHomo sapiens
567uaauacugcc ggguaaugau gga
2356823RNAHomo sapiens 568agcuacauug ucugcugggu uuc
2356923RNAHomo sapiens 569ucgaggacug guggaagggc cuu
2357023RNAHomo sapiens
570cugacugaau agguaggguc auu
2357123RNAHomo sapiens 571cugauaagaa cagaggccca gau
2357223RNAHomo sapiens 572ccugggcagc guguggcuga agg
2357323RNAHomo sapiens
573ucugggaggu uguagcagug gaa
2357423RNAHomo sapiens 574agggacugcc uuaggagaaa guu
2357523RNAHomo sapiens 575ucccuguccu ccaggagcuc acg
2357623RNAHomo sapiens
576ucucacacag aaaucgcacc cgu
2357723RNAHomo sapiens 577ugucugcccg caugccugcc ucu
2357823RNAHomo sapiens 578ccacuuggau cugaaggcug ccc
2357923RNAHomo sapiens
579cgagggcauu ucaugaugca ggc
2358023RNAHomo sapiens 580caucagcacc cuauguccuu ucu
2358123RNAHomo sapiens 581ugagcaccac acaggccggg cgc
2358223RNAHomo sapiens
582accuggaccc agcguagaca aag
2358323RNAHomo sapiens 583ucaaggccag aggucccaca gca
2358423RNAHomo sapiens 584uucgggcugg ccugcugcuc cgg
2358523RNAHomo sapiens
585agguuacccg agcaacuuug cau
2358623RNAHomo sapiens 586aucaacagac auuaauuggg cgc
2358723RNAHomo sapiens 587aaugacacga ucacucccgu uga
2358823RNAHomo sapiens
588ucuuggagua ggucauuggg ugg
2358923RNAHomo sapiens 589gauugagacu aguagggcua ggc
2359023RNAHomo sapiens 590uagugcaaua uugcuuauag ggu
2359123RNAHomo sapiens
591uggaguuaag gguugcuugg aga
2359223RNAHomo sapiens 592uugcauguca gauuguaauu ccc
2359323RNAHomo sapiens 593agggaaaaaa aaaaggauuu guc
2359423RNAHomo sapiens
594uggagaucca gugcucgccc gau
2359523RNAHomo sapiens 595uaucugcugg gcuuucuggu guu
2359623RNAHomo sapiens 596ggcaggaggg cugugccagg uug
2359723RNAHomo sapiens
597agggccagag gagccuggag ugg
2359823RNAHomo sapiens 598cuggcggagc ccauuccaug cca
2359923RNAHomo sapiens 599uguagagcag ggagcaggaa gcu
2360023RNAHomo sapiens
600ucaggcaaag ggauauuuac aga
2360123RNAHomo sapiens 601uggccggaug ggacaggagg cau
2360223RNAHomo sapiens 602uggcccggcg acgucucacg guc
2360323RNAHomo sapiens
603ccggucccag gagaaccugc aga
2360423RNAHomo sapiens 604augcggaccu ggguuagcgg agu
2360523RNAHomo sapiens 605cagggaggcg cucacucucu gcu
2360623RNAHomo sapiens
606cgcgggcgcu ccuggccgcc gcc
2360723RNAHomo sapiens 607aggaccugcg ggacaagauu cuu
2360823RNAHomo sapiens 608uaauccuugc uaccugggug aga
2360923RNAHomo sapiens
609ucacaacaac cuugcagggu aga
2361023RNAHomo sapiens 610uagcagcggg aacaguucug cag
2361123RNAHomo sapiens 611uacuccagag ggcgucacuc aug
2361223RNAHomo sapiens
612ggguuuguag cuuugcuggc aug
2361323RNAHomo sapiens 613augcuacucg gaaaucccac uga
2361423RNAHomo sapiens 614aaucggaccc auuuaaaccg gag
2361523RNAHomo sapiens
615ugcacauggc aaccuagcuc cca
2361623RNAHomo sapiens 616uaaaucccau ggugccuucu ccu
2361723RNAHomo sapiens 617acuugggcac ugaaacaaug ucc
2361823RNAHomo sapiens
618acugggaugu cacugaauau ggu
2361923RNAHomo sapiens 619uuugggauug acgccacaug ucu
2362023RNAHomo sapiens 620ggcagguucu cacccucucu agg
2362123RNAHomo sapiens
621ugucacucgg cucggcccac uac
2362223RNAHomo sapiens 622aaggagcuua caaucuagcu ggg
2362323RNAHomo sapiens 623uccaguacca cgugucaggg cca
2362423RNAHomo sapiens
624cgggucggag uuagcucaag cgg
2362523RNAHomo sapiens 625agguugggau cgguugcaau gcu
2362623RNAHomo sapiens 626cacccggcug ugugcacaug ugc
2362723RNAHomo sapiens
627gcuucuccug gcucuccucc cuc
2362823RNAHomo sapiens 628cucucaccac ugcccuccca cag
2362923RNAHomo sapiens 629ccucagggcu guagaacagg gcu
2363023RNAHomo sapiens
630guccaguuuu cccaggaauc ccu
2363123RNAHomo sapiens 631cggcccgggc ugcugcuguu ccu
2363223RNAHomo sapiens 632aucagggcuu guggaauggg aag
2363323RNAHomo sapiens
633uuuugcauga cccugggagu agg
2363423RNAHomo sapiens 634agggcauagg agaggguuga uau
2363523RNAHomo sapiens 635ugacacggag gguggcuugg gaa
2363623RNAHomo sapiens
636gagggcagcg uggguguggc gga
2363723RNAHomo sapiens 637ugggcugagg gcaggaggcc ugu
2363823RNAHomo sapiens 638cagggcucag ggauuggaug gag
2363923RNAHomo sapiens
639gacacgggcg acagcugcgg ccc
2364023RNAHomo sapiens 640ugugcuugcu cgucccgccc gca
2364123RNAHomo sapiens 641uggugcggag agggcccaca gug
2364223RNAHomo sapiens
642ugacaccugc cacccagccc aag
2364323RNAHomo sapiens 643gagggucuug ggagggaugu gac
2364423RNAHomo sapiens 644ugggccaggg agcagcuggu ggg
2364524RNAHomo sapiens
645uggcccugac ugaagaccag cagu
2464624RNAHomo sapiens 646uugcagcugc cugggaguga cuuc
2464724RNAHomo sapiens 647agcgcgggcu gagcgcugcc
aguc 2464824RNAHomo sapiens
648uggguagaga aggagcucag agga
2464924RNAHomo sapiens 649uguggacagu gagguagagg gagu
2465024RNAHomo sapiens 650cauagcccgg ucgcugguac
auga 2465124RNAHomo sapiens
651cccggacagg cguucgugcg acgu
2465224RNAHomo sapiens 652guggaaagca ugcauccagg gugu
2465324RNAHomo sapiens 653ugcccaugcc auacuuuugc
cuca 2465424RNAHomo sapiens
654agaggacccg uagcugcuag aagg
2465524RNAHomo sapiens 655ggugggaugg agagaaggua ugag
2465624RNAHomo sapiens 656acauccugcu ccacagggca
gagg 2465724RNAHomo sapiens
657agggcuggac ucagcggcgg agcu
2465824RNAHomo sapiens 658ucugggcaca ggcggaugga cagg
2465924RNAHomo sapiens 659ucagaacaaa ugccgguucc
caga 2466024RNAHomo sapiens
660gaccuggaca uguuugugcc cagu
2466124RNAHomo sapiens 661ugccuggguc ucuggccugc gcgu
2466224RNAHomo sapiens 662aaagugccgc cuaguuuuaa
gccc 2466324RNAHomo sapiens
663ucccugagac ccuuuaaccu guga
2466424RNAHomo sapiens 664agcagaagca gggagguucu ccca
2466524RNAHomo sapiens 665gguugggcag ugaggagggu
guga 2466624RNAHomo sapiens
666acaaaaaaaa aagcccaacc cuuc
2466724RNAHomo sapiens 667ucccugagga gcccuuugag ccug
2466825RNAHomo sapiens 668gggcgacaaa gcaagacucu
uucuu 2566925RNAHomo sapiens
669ggcggaggga aguagguccg uuggu
2567025RNAHomo sapiens 670cuagugaggg acagaaccag gauuc
2567125RNAHomo sapiens 671ugggaacggg uuccggcaga
cgcug 2567225RNAHomo sapiens
672gcugggcagg gcuucugagc uccuu
2567325RNAHomo sapiens 673agggaucgcg ggcggguggc ggccu
2567426RNAHomo sapiens 674gcucagggau gauaacugug
cugaga 2667527RNAHomo sapiens
675cacuguaggu gauggugaga gugggca
2767617RNAHomo sapiens 676ggggcgcggc cggaucg
1767717RNAHomo sapiens 677ccccgccacc gccuugg
1767817RNAHomo sapiens
678uggggcucag cgaguuu
1767917RNAHomo sapiens 679accccacucc ugguacc
1768017RNAHomo sapiens 680gggguggucu guuguug
1768117RNAHomo sapiens
681ggauggagga ggggucu
1768217RNAHomo sapiens 682gagacugggg uggggcc
1768317RNAHomo sapiens 683ggggcugggc gcgcgcc
1768417RNAHomo sapiens
684gcggggcugg gcgcgcg
1768517RNAHomo sapiens 685gggagaaggg ucggggc
1768617RNAHomo sapiens 686ccccggggag cccggcg
1768718RNAHomo sapiens
687agcaggugcg gggcggcg
1868818RNAHomo sapiens 688ccagaggugg ggacugag
1868918RNAHomo sapiens 689cagccccaca gccucaga
1869018RNAHomo sapiens
690acaggcagga uuggggaa
1869118RNAHomo sapiens 691aucucgcugg ggccucca
1869218RNAHomo sapiens 692cggggcggca ggggccuc
1869318RNAHomo sapiens
693gggcucacau caccccau
1869418RNAHomo sapiens 694ccccugggcc ggccuugg
1869518RNAHomo sapiens 695gggugcgggc cggcgggg
1869619RNAHomo sapiens
696uggggcggag cuuccggag
1969719RNAHomo sapiens 697ggccuuguuc cugucccca
1969819RNAHomo sapiens 698ugucucugcu gggguuucu
1969919RNAHomo sapiens
699cagcaggagg ugaggggag
1970019RNAHomo sapiens 700acuugagggg caugaggau
1970119RNAHomo sapiens 701ggggccuggc ggugggcgg
1970219RNAHomo sapiens
702cuuggggcau ggaguccca
1970319RNAHomo sapiens 703cggcgcgacc ggcccgggg
1970419RNAHomo sapiens 704agcagggcug gggauugca
1970519RNAHomo sapiens
705ggggagcgag gggcggggc
1970620RNAHomo sapiens 706cuuccucguc ugucugcccc
2070720RNAHomo sapiens 707uuggccaugg ggcugcgcgg
2070820RNAHomo sapiens
708ucuggccagc uacgucccca
2070920RNAHomo sapiens 709acugccccag gugcugcugg
2071020RNAHomo sapiens 710gguauccguu uggggauggu
2071120RNAHomo sapiens
711ggcuccuugg ucuaggggua
2071220RNAHomo sapiens 712gcggagagag aauggggagc
2071320RNAHomo sapiens 713accaggaggc ugaggccccu
2071420RNAHomo sapiens
714ggggagcugu ggaagcagua
2071520RNAHomo sapiens 715cgugccaccc uuuuccccag
2071620RNAHomo sapiens 716cgcgggucgg ggucugcagg
2071720RNAHomo sapiens
717aaaaggcggg agaagcccca
2071820RNAHomo sapiens 718cggcucuggg ucugugggga
2071920RNAHomo sapiens 719ccccagggcg acgcggcggg
2072020RNAHomo sapiens
720guggguuggg gcgggcucug
2072120RNAHomo sapiens 721ucagggaguc aggggagggc
2072220RNAHomo sapiens 722cggggugggu gaggucgggc
2072320RNAHomo sapiens
723gggcuggggc gcggggaggu
2072420RNAHomo sapiens 724ggugggaggu ggggugggca
2072521RNAHomo sapiens 725ccccaccucc ucucuccuca g
2172621RNAHomo sapiens
726ccuguugaag uguaaucccc a
2172721RNAHomo sapiens 727cggcggggac ggcgauuggu c
2172821RNAHomo sapiens 728auccccagau acaauggaca a
2172921RNAHomo sapiens
729ugcacggcac uggggacacg u
2173021RNAHomo sapiens 730aggggugcua ucugugauug a
2173121RNAHomo sapiens 731uggggcuagu gaugcaggac g
2173221RNAHomo sapiens
732ucugaggccu gccucucccc a
2173321RNAHomo sapiens 733gagguuuggg gaggauuugc u
2173421RNAHomo sapiens 734uagcggggau uccaauauug g
2173521RNAHomo sapiens
735cggggcagcu caguacagga u
2173621RNAHomo sapiens 736uacuuuucua gguuguuggg g
2173721RNAHomo sapiens 737gguggggcaa ugggaucagg u
2173821RNAHomo sapiens
738gccccugggc cuauccuaga a
2173921RNAHomo sapiens 739agccgcgggg aucgccgagg g
2174021RNAHomo sapiens 740cugugggcuc agcgcguggg g
2174121RNAHomo sapiens
741ucccuccuuc uguccccaca g
2174221RNAHomo sapiens 742guuggggugc aggggucugc u
2174321RNAHomo sapiens 743gccccgggca gugugaucau c
2174421RNAHomo sapiens
744cguccccgcu cggcgggguc c
2174521RNAHomo sapiens 745uggcagggag gcugggaggg g
2174621RNAHomo sapiens 746gcccuccgcc cgugcacccc g
2174721RNAHomo sapiens
747ucccuacccc uccacucccc a
2174821RNAHomo sapiens 748cccuuggguc ugauggggua g
2174921RNAHomo sapiens 749acccucguca gguccccggg g
2175021RNAHomo sapiens
750ugcccacccu uuaccccgcu c
2175122RNAHomo sapiens 751caaauucgua ucuaggggaa ua
2275222RNAHomo sapiens 752acagauucga uucuagggga au
2275322RNAHomo sapiens
753ccucuucccc uugucucucc ag
2275422RNAHomo sapiens 754uuuagagacg gggucuugcu cu
2275522RNAHomo sapiens 755ucaaaacuga ggggcauuuu cu
2275622RNAHomo sapiens
756uuuggucccc uucaaccagc ug
2275722RNAHomo sapiens 757uuuggucccc uucaaccagc ua
2275822RNAHomo sapiens 758ugugacuggu ugaccagagg gg
2275922RNAHomo sapiens
759aggggcuggc uuuccucugg uc
2276022RNAHomo sapiens 760gcugcgcuug gauuucgucc cc
2276122RNAHomo sapiens 761ccaguggggc ugcuguuauc ug
2276222RNAHomo sapiens
762gguccagagg ggagauaggu uc
2276322RNAHomo sapiens 763uuggggaaac ggccgcugag ug
2276422RNAHomo sapiens 764ugucaguuug ucaaauaccc ca
2276522RNAHomo sapiens
765uguaaacauc cccgacugga ag
2276622RNAHomo sapiens 766uccccuucug caggccugcu gg
2276722RNAHomo sapiens 767aggggaccaa agagauauau ag
2276822RNAHomo sapiens
768cuggggagau ccucgagguu gg
2276922RNAHomo sapiens 769caaccucgag gaucucccca gc
2277022RNAHomo sapiens 770uguguuagaa uaggggcaau aa
2277122RNAHomo sapiens
771cugggguucu gagacagaca gu
2277222RNAHomo sapiens 772cggggagaga acgcagugac gu
2277322RNAHomo sapiens 773agaaggggug aaauuuaaac gu
2277422RNAHomo sapiens
774uggggcggag cuuccggagg cc
2277522RNAHomo sapiens 775guggaguccu ggggaaugga ga
2277622RNAHomo sapiens 776uuaucagaau cuccaggggu ac
2277722RNAHomo sapiens
777uaaugccccu aaaaauccuu au
2277822RNAHomo sapiens 778gccugcuggg guggaaccug gu
2277922RNAHomo sapiens 779gaaggcagca gugcuccccu gu
2278022RNAHomo sapiens
780uaaggggugu auggcagaug ca
2278122RNAHomo sapiens 781gaauguugcu cggugaaccc cu
2278222RNAHomo sapiens 782ugucgugggg cuugcuggcu ug
2278322RNAHomo sapiens
783uggggauuug gagaaguggu ga
2278422RNAHomo sapiens 784cucaaguagu cugaccaggg ga
2278522RNAHomo sapiens 785uuucuauuuc ucaguggggc uc
2278622RNAHomo sapiens
786auggcaucgu ccccuggugg cu
2278722RNAHomo sapiens 787aggggacugg uuaauagaac ua
2278822RNAHomo sapiens 788cuuccggucu gugagccccg uc
2278922RNAHomo sapiens
789acuggggagc agaaggagaa cc
2279022RNAHomo sapiens 790ggggcuguga uugaccagca gg
2279122RNAHomo sapiens 791ucuggggaug aggacagugu gu
2279222RNAHomo sapiens
792uuggccacca caccuacccc uu
2279322RNAHomo sapiens 793aacucugacc ccuuagguug au
2279422RNAHomo sapiens 794uccuguacug agcugccccg ag
2279522RNAHomo sapiens
795aaccccuaag gcaacuggau gg
2279622RNAHomo sapiens 796aaccagcacc ccaacuuugg ac
2279722RNAHomo sapiens 797uuggaauagg ggauaucuca gc
2279822RNAHomo sapiens
798cagcagggga gagagaggag uc
2279922RNAHomo sapiens 799aggcgaugug gggauguaga ga
2280022RNAHomo sapiens 800auaguccgag uaacgucggg gc
2280122RNAHomo sapiens
801acuccagccc cacagccuca gc
2280222RNAHomo sapiens 802aggcagcggg guguagugga ua
2280322RNAHomo sapiens 803ccaagucuug gggagaguug ag
2280422RNAHomo sapiens
804uauucauuua cuccccagcc ua
2280522RNAHomo sapiens 805ucggccugac cacccacccc ac
2280622RNAHomo sapiens 806aagcccuuac cccaaaaagu au
2280722RNAHomo sapiens
807aagcccuuac cccaaaaagc au
2280822RNAHomo sapiens 808cucggcgcgg ggcgcgggcu cc
2280922RNAHomo sapiens 809ugcccuaaau gccccuucug gc
2281022RNAHomo sapiens
810cgcaggggcc gggugcucac cg
2281122RNAHomo sapiens 811cgggguuuug agggcgagau ga
2281222RNAHomo sapiens 812cagaagggga guugggagca ga
2281322RNAHomo sapiens
813cugccagccc cguuccaggg ca
2281422RNAHomo sapiens 814caguuggguc uaggggucag ga
2281522RNAHomo sapiens 815cgucccgggg cugcgcgagg ca
2281622RNAHomo sapiens
816guucuguuaa cccauccccu ca
2281722RNAHomo sapiens 817caccggggau ggcagagggu cg
2281822RNAHomo sapiens 818uggggugccc acuccgcaag uu
2281922RNAHomo sapiens
819uaggggcagc agaggaccug gg
2282022RNAHomo sapiens 820agcccgcccc agccgagguu cu
2282122RNAHomo sapiens 821cccucucugg cuccucccca aa
2282222RNAHomo sapiens
822uggggaaggc gucagugucg gg
2282322RNAHomo sapiens 823ugcggggaca ggccagggca uc
2282422RNAHomo sapiens 824ucugccaucc ucccuccccu ac
2282522RNAHomo sapiens
825ucaggcucag uccccucccg au
2282622RNAHomo sapiens 826aguggggaac ccuuccauga gg
2282722RNAHomo sapiens 827ugaggcccuu ggggcacagu gg
2282822RNAHomo sapiens
828uuuugugucu cccauucccc ag
2282922RNAHomo sapiens 829ugagggguuu ggaaugggau gg
2283022RNAHomo sapiens 830aggcggggcg ccgcgggacc gc
2283122RNAHomo sapiens
831ugcggggcua gggcuaacag ca
2283222RNAHomo sapiens 832ggguggggau uuguugcauu ac
2283322RNAHomo sapiens 833acccgucccg uucguccccg ga
2283422RNAHomo sapiens
834ggaggggucc cgcacuggga gg
2283522RNAHomo sapiens 835gggguuccug gggaugggau uu
2283622RNAHomo sapiens 836cuugguucag ggaggguccc ca
2283722RNAHomo sapiens
837ugcagggguc gggugggcca gg
2283822RNAHomo sapiens 838gggacccggg gagagaugua ag
2283922RNAHomo sapiens 839ggggcugggg ccgggacaga gc
2284022RNAHomo sapiens
840agggaagggg acgaggguug gg
2284123RNAHomo sapiens 841uuaaugcuaa ucgugauagg ggu
2384223RNAHomo sapiens 842aaagucucgc ucucugcccc uca
2384323RNAHomo sapiens
843agaggcuuug ugcggauacg ggg
2384423RNAHomo sapiens 844uggggacgua gcuggccaga cag
2384523RNAHomo sapiens 845uauggggcuu cuguagagau uuc
2384623RNAHomo sapiens
846gaagugcuuc gauuuugggg ugu
2384723RNAHomo sapiens 847agcucggucu gaggccccuc agu
2384823RNAHomo sapiens 848ugaggggcag agagcgagac uuu
2384923RNAHomo sapiens
849ucaaaaugua gaggaagacc cca
2385023RNAHomo sapiens 850uguuucgggg cucauggccu gug
2385123RNAHomo sapiens 851aggucugcau ucaaaucccc aga
2385223RNAHomo sapiens
852caggcagaag uggggcugac agg
2385323RNAHomo sapiens 853ccucaccacc ccuucugccu gca
2385423RNAHomo sapiens 854ucugcucaua ccccaugguu ucu
2385523RNAHomo sapiens
855uccggggcug aguucugugc acc
2385623RNAHomo sapiens 856ggggaaagcg aguagggaca uuu
2385723RNAHomo sapiens 857cgcauccccu agggcauugg ugu
2385823RNAHomo sapiens
858ugaggauaug gcagggaagg gga
2385923RNAHomo sapiens 859ugggagggga gaggcagcaa gca
2386023RNAHomo sapiens 860cgggcugucc ggaggggucg gcu
2386123RNAHomo sapiens
861ugccccaccu gcugaccacc cuc
2386223RNAHomo sapiens 862gugaguggga gccggugggg cug
2386323RNAHomo sapiens 863ccccgguguu ggggcgcguc ugc
2386423RNAHomo sapiens
864ccggggcaga uugguguagg gug
2386523RNAHomo sapiens 865gcgaggaccc cucggggucu gac
2386623RNAHomo sapiens 866aggaagcccu ggaggggcug gag
2386723RNAHomo sapiens
867ugggcagggg cuuauuguag gag
2386823RNAHomo sapiens 868cugggaucuc cggggucuug guu
2386923RNAHomo sapiens 869uuagggagua gaaggguggg gag
2387023RNAHomo sapiens
870gccccggcgc gggcggguuc ugg
2387123RNAHomo sapiens 871ugaguggggc ucccgggacg gcg
2387223RNAHomo sapiens 872aucccuugca ggggcuguug ggu
2387323RNAHomo sapiens
873cugggcccgc ggcgggcgug ggg
2387424RNAHomo sapiens 874ugaggggccu cagaccgagc uuuu
2487524RNAHomo sapiens 875ugucagugac uccugccccu
uggu 2487624RNAHomo sapiens
876uuggacuuuu ucagauuugg ggau
2487724RNAHomo sapiens 877cugcaggcag aaguggggcu gaca
2487824RNAHomo sapiens 878ucuguagccu gggagcaaug
gggu 2487924RNAHomo sapiens
879gaugcgccgc ccacugcccc gcgc
2488024RNAHomo sapiens 880ugggcgaggg gugggcucuc agag
2488124RNAHomo sapiens 881aggcaggggc uggugcuggg
cggg 2488224RNAHomo sapiens
882ggaggccggg guggggcggg gcgg
2488325RNAHomo sapiens 883cuuccagacg cuccgcccca cgucg
2588425RNAHomo sapiens 884agcggggagg aagugggcgc
ugcuu 2588525RNAHomo sapiens
885caugcugacc ucccuccugc cccag
2588625RNAHomo sapiens 886agggguggug uugggacagc uccgu
2588725RNAHomo sapiens 887ugccccaucu gugcccuggg
uagga 2588825RNAHomo sapiens
888aagggaggag gagcggaggg gcccu
2588926RNAHomo sapiens 889cacaggacug acuccucacc ccagug
2689026RNAHomo sapiens 890gugagggcau gcaggccugg
augggg 2689126RNAHomo sapiens
891cccagggcuu ggaguggggc aagguu
2689217RNAHomo sapiens 892gugggggaga ggcuguc
1789317RNAHomo sapiens 893ggugggggcu guuguuu
1789417RNAHomo sapiens
894ggcgggugcg ggggugg
1789518RNAHomo sapiens 895cgggcguggu gguggggg
1889618RNAHomo sapiens 896agggcauguc cagggggu
1889718RNAHomo sapiens
897cagcaguccc ucccccug
1889818RNAHomo sapiens 898cuaggggguu ugcccuug
1889918RNAHomo sapiens 899agggggcggg cuccggcg
1890019RNAHomo sapiens
900ggcuugcaug ggggacugg
1990119RNAHomo sapiens 901gggggaagaa aaggugggg
1990219RNAHomo sapiens 902aaggggcugg gggagcaca
1990320RNAHomo sapiens
903uaggaugggg gugagaggug
2090420RNAHomo sapiens 904ccguguuucc cccacgcuuu
2090520RNAHomo sapiens 905acucaaacug ugggggcacu
2090620RNAHomo sapiens
906ggcggcggcg gaggcggggg
2090720RNAHomo sapiens 907cgccccuccu gcccccacag
2090820RNAHomo sapiens 908gggaaaagga agggggagga
2090920RNAHomo sapiens
909agcccccugg ccccaaaccc
2091020RNAHomo sapiens 910ugggaauggg gguaagggcc
2091121RNAHomo sapiens 911gugccagcug caguggggga g
2191221RNAHomo sapiens
912uccuucugcu ccguccccca g
2191321RNAHomo sapiens 913uggcuguugg agggggcagg c
2191421RNAHomo sapiens 914auccaguucu cugagggggc u
2191521RNAHomo sapiens
915agggggaaag uucuauaguc c
2191621RNAHomo sapiens 916cuccgugcac acccccgcgu g
2191721RNAHomo sapiens 917cagugcaauu aaaaggggga a
2191821RNAHomo sapiens
918gugggcgggg gcaggugugu g
2191921RNAHomo sapiens 919acaggagugg gggugggaca u
2192021RNAHomo sapiens 920gggcaucugc ugacaugggg g
2192121RNAHomo sapiens
921agggagggac gggggcugug c
2192221RNAHomo sapiens 922gggcuagggc cugcugcccc c
2192321RNAHomo sapiens 923aaggcagggc ccccgcuccc c
2192422RNAHomo sapiens
924cugguacagg ccugggggac ag
2292522RNAHomo sapiens 925ucugcccccu ccgcugcugc ca
2292622RNAHomo sapiens 926uuuaacaugg ggguaccugc ug
2292722RNAHomo sapiens
927caucucuaag gaacuccccc aa
2292822RNAHomo sapiens 928acucaaaaug ggggcgcuuu cc
2292922RNAHomo sapiens 929uugaggagac augguggggg cc
2293022RNAHomo sapiens
930agggggcgca gucacugacg ug
2293122RNAHomo sapiens 931aagggggaag gaaacaugga ga
2293222RNAHomo sapiens 932uccauguuuc cuucccccuu cu
2293322RNAHomo sapiens
933cacacaagug gcccccaaca cu
2293422RNAHomo sapiens 934ugcugggggc cacaugagug ug
2293522RNAHomo sapiens 935agggggaugg cagagcaaaa uu
2293622RNAHomo sapiens
936ugggggagug cagugauugu gg
2293722RNAHomo sapiens 937gacuauagaa cuuucccccu ca
2293822RNAHomo sapiensmisc_feature"n" is abasic or
substituted base 938acucaaacua ugggggcacu uu
2293922RNAHomo sapiens 939acucaaacug ggggcucuuu ug
2294022RNAHomo sapiens
940ugagccccug ugccgccccc ag
2294122RNAHomo sapiens 941cacccccugu uuccuggccc ac
2294222RNAHomo sapiens 942gcgggggugg cggcggcauc cc
2294322RNAHomo sapiens
943gggggucccc ggugcucgga uc
2294422RNAHomo sapiens 944ccugacccac ccccucccgc ag
2294523RNAHomo sapiens 945ucccccaggu gugauucuga uuu
2394623RNAHomo sapiens
946acaggcggcu guagcaaugg ggg
2394723RNAHomo sapiens 947uagcccccag gcuucacuug gcg
2394823RNAHomo sapiens 948cugggggacg cgugagcgcg agc
2394923RNAHomo sapiens
949uuucaagcca gggggcguuu uuc
2395024RNAHomo sapiens 950ugggggagcc augagauaag agca
2495124RNAHomo sapiens 951acugggggcu uucgggcucu
gcgu 2495224RNAHomo sapiens
952uggggagcug aggcucuggg ggug
2495325RNAHomo sapiens 953cccccacaac cgcgcuugac uagcu
2595426RNAHomo sapiens 954cucggccgcg gcgcguagcc
cccgcc 2695518RNAHomo sapiens
955gguggggggu guuguuuu
1895618RNAHomo sapiens 956gggucccggg gagggggg
1895720RNAHomo sapiens 957ucacaccugc cucgcccccc
2095820RNAHomo sapiens
958ucucuucauc uaccccccag
2095921RNAHomo sapiens 959ggggggaugu gcaugcuggu u
2196021RNAHomo sapiens 960cgucccaccc cccacuccug u
2196122RNAHomo sapiens
961cuucccccca guaaucuuca uc
2296222RNAHomo sapiens 962guggguacgg cccagugggg gg
2296318RNAHomo sapiens 963ugaggcgggg gggcgagc
1896420RNAHomo sapiens
964agagaugaag cgggggggcg
2096521RNAHomo sapiens 965agggcccccc cucaauccug u
2196622RNAHomo sapiens 966acgcccuucc cccccuucuu ca
2296722DNAArtificial
Sequenceprobe 967tcgccctctc aacccagctt tt
2296822DNAArtificial Sequenceprobemisc_feature(14)..(14)"n"
is abasic 968tcgccctctc aacncagctt tt
2296922DNAArtificial Sequenceprobemisc_feature(5)..(5)"n" is
abasic 969tcgcnctctc aacccagctt tt
2297022DNAArtificial Sequenceprobemisc_feature(5)..(5)"n" is
abasicmisc_feature(14)..(14)"n" is abasic 970tcgcnctctc aacncagctt tt
2297122RNAArtificial
Sequencetarget sequence 971aaaagcuggg uugagagggc ga
2297221RNAArtificial Sequencenon-target sequence
972uggcagggag gcugggaggg g
2197323RNAArtificial Sequencetarget sequence 973agcuacauug ucugcugggu uuc
2397421RNAArtificial
Sequencenon-target sequence 974uggcagggag gcugggaggg g
2197523DNAArtificial Sequenceprobe
975gaaacccagc agacaatgta gct
2397618DNAArtificial Sequenceprobe 976ccagcagaca atgtagct
1897717DNAArtificial Sequenceprobe
977cagcagacaa tgtagct
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